Integrated cold therapy and electrical stimulation systems for locating and treating nerves and associated methods

ABSTRACT

The present invention generally relates to improved medical devices, systems, and methods. In many embodiments, devices, systems, and methods for locating and treating a target nerve with integrated cold therapy and electrical stimulation systems are provided. For example, nerve stimulation and cryoneurolysis may be delivered concurrently or alternately with the cryo-stimulation device. In some embodiments, the device may be operated by a single operator or clinician. Accordingly, embodiments of the present disclosure may improve nerve targeting during cryoneurolysis procedures. Improvements in nerve localization and targeting may increase treatment accuracy, physician confidence in needle placement during treatment, and clinical efficacy and safety. In turn, such improvements may decrease overall treatment times, the number of repeat treatments, and the re-treatment rate. Further, additional improvements in nerve localization and targeting may reduce the number of needle insertions, applied treatment cycles, and may also reduce the number of cartridge changes.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application claims the benefit of U.S. Provisional Application Ser. No. 62/586,625, filed Nov. 15, 2017, which is incorporated by reference herein in its entirety for all purposes.

The present application is related to U.S. application Ser. No. 15/594,238 filed May 12, 2017, entitled “METHODS AND SYSTEMS FOR LOCATING AND TREATING NERVES WITH COLD THERAPY”, which is assigned to the same assignee as the present application, and the full disclosure of which is incorporated herein by reference in its entirety for all purposes.

BACKGROUND

The present invention generally related to improved medical devices, systems, and methods. In many embodiments, devices, systems, and methods for locating and treating a nerve with integrated cold therapy and electrical stimulation systems are provided.

Cryoneurolysis or cryoneuroablation may be used to treat nerves to temporarily stop nerve signaling, typically for a set period of time, and may be followed by a restoration of nerve function. Cryoneurolysis can be used on motor nerves for various cosmetic applications and/or medical conditions, including but not limited to: movement disorders, muscle spasms, muscle hyperactivity and/or any condition where reduction in muscle movement is desired. Additionally, Cryoneurolysis may be used on sensory nerves to provide temporary or permanent pain relief by degenerating the nerve and providing a peripheral nerve block. While Cryoneurolysis has many beneficial applications, further improvements in the methods, devices, and systems may be had.

SUMMARY

The present invention generally relates to improved medical devices, systems, and methods. In many embodiments, devices, systems, and methods for locating and treating a target nerve with integrated cold therapy and electrical stimulation systems are provided. For example, nerve stimulation and cryoneurolysis may be delivered concurrently or alternately with the cryo-stimulation device. Further, in some embodiments, the device may be operated by a single operator or clinician. In yet other embodiments, manufacturability may be improved or costs decreased. In other embodiments, ease of assembly may also be improved. Accordingly, such embodiments of the present disclosure may improve nerve targeting during cryoneurolysis procedures. Improvements in nerve localization and targeting may increase treatment accuracy and physician confidence in needle placement during treatment. In turn, such improvements may decrease overall treatment times, the number of repeat treatments, and the re-treatment rate. Further, additional improvements in nerve localization and targeting may reduce the number of needle insertions, applied treatment cycles, and may also reduce the number of cartridge changes (when replaceable refrigerant cartridges are used). Thus, embodiments of the present disclosure may provide one or more advantages for cryoneurolysis by improving localization and treatment of target nerves. Hence, some aspects of the present disclosure provide methods, devices, and systems for localizing, targeting, and treating a nerve with integrated cold therapy and electrical stimulation systems.

In some embodiments, a cryo-stimulation treatment device may be provided that includes a needle assembly having a proximal portion and a distal portion. The needle assembly may be configured to produce a cold zone for cryoneurolysis of a target nerve. The device includes first and second electrical contacts coupled to the distal portion of the needle assembly and configured to be electrically coupled to an electrical nerve stimulation generator to provide bipolar stimulation, using either biphasic or monophasic stimulation signals. The electrical nerve stimulation generator is configured to generate a first electric field about the first and second electrical contacts for electrically stimulating and locating the target nerve.

In some embodiments, a treatment device includes a handle defined by a housing coupled to the proximal portion of the needle assembly. The electrical nerve stimulation generator may be disposed within the handle housing. In other embodiments, an external electrical nerve stimulation generator is coupled to an electrical port on the handle housing or the needle assembly. In some aspects, the second electrical contact (e.g., return electrode) is an anode and the first electrical contact (e.g., active or stimulating electrode closest to nerve being stimulated) is a cathode.

In certain embodiments, the treatment device further includes a third electrical contact spaced apart from the needle assembly and configured to be electrically coupled to the electrical nerve stimulation generator and at least one of the first or second electrical contacts to provide monopolar stimulation. The electrical nerve stimulation generator is configured to generate a second electric field about the third electrical contact and the at least one of the first or second electrical contacts for electrically stimulating and locating the target nerve. In some embodiments, the third electrical contact serves as a return electrode and the at least one of the first or second electrical contacts serves as an active electrode. In some aspects, third electrical contact is configured to be positioned on skin of a patient (e.g., patient's leg or back), a housing of the treatment device, or a heater block of the treatment device.

In some embodiments, the second electric field is generated prior to the first electric field. It may be advantageous generate the second monopolar electric field initially for gross positioning and then switch to the first bipolar stimulation to fine-tune the positioning of the needle. In some aspects, the first and second electrical contacts are located asymmetrically on the needle assembly. In some embodiments, a distal end of the needle assembly comprises a beveled edge. In some aspects, the first electrical contact extends along the beveled edge. In some aspects, only a distal tip of the beveled edge is electrically conductive.

In certain embodiments, a contact surface area of the second electrical contact is greater than a contact surface area of the first electrical contact. In some aspects, the first and second electrical contacts face opposing directions. In some aspects, the first and second electrical contacts comprise concave-shaped, convex-shaped, or round-shaped electrodes. In some embodiments, the needle assembly comprises at least one or more needles and the two or more electrical contracts may reside on or within the same or separate needles. Still further, the electrical contacts may reside on or within the needle, heater assembly, and/or housing of the needle assembly and function as either an active or return electrode.

In certain embodiments, a cryo-stimulation treatment device is provided that includes a needle assembly configured to produce a cold zone for cryoneurolysis of a target nerve. The needle assembly includes a first shaft constructed of electrically conductive material and including an electrically insulating coating. The first shaft includes a proximal end, a distal end, and length therebetween. The proximal end of the first shaft is couplable with an electrical nerve stimulation generator that generates an electric field for electrically stimulating and locating the target nerve. The device further includes a second shaft comprising a proximal end, a distal end, and a shaft lumen extending therebetween. The second shaft further includes a cooling fluid supply lumen extending distally within the shaft lumen to a distal portion of the shaft lumen of the second shaft.

In some aspects, the first shaft is retractable relative to the second shaft. In certain aspects, the distal ends of the first shaft and the second shaft form a beveled distal end of the needle.

In further embodiments, the device further includes a third shaft. The third shaft includes a proximal end, a distal end, and a shaft lumen extending therebetween. The second shaft and third shaft extend axially along opposing sides of the first shaft. According to certain aspects, the first shaft is retractable relative to the second shaft and the third shaft.

In yet further embodiments, the device includes a heating element and a sensor or heater block may be coupled to the heating element that acts as electrical return during electrical nerve stimulation of the target nerve. In some embodiments, the device further includes a housing and the housing acts as electrical return during electrical nerve stimulation of the target nerve. In some aspects as discussed herein, the sensor, heater block, or housing may function as either the return or active electrode.

In some embodiments, a distal end portion of the first shaft is uninsulated by the electrically insulating coating such that the electric field is generated only about the distal end portion of the first shaft to stimulate the target nerve. In certain aspects, only a tip of the distal end portion is uninsulated by the electrically insulating coating.

In certain embodiments, the device further includes a cooling fluid source couplable to the cooling fluid supply lumen to direct cooling fluid flow into the second shaft lumen so that liquid from the cooling fluid flow vaporizes within the second shaft lumen to produce the cold zone. In further aspects, the first and second shafts extend contiguously.

In further embodiments, a cryo-stimulation treatment device is provided that includes a needle assembly having a proximal portion and a distal portion, the needle assembly configured to produce a cold zone for cryoneurolysis of a target nerve. The device includes a first electrical contact coupled to the distal portion of the needle assembly and a second electrical contact positioned on a heater assembly of the needle assembly configured to serve as a return electrode. The first and second electrical contacts are configured to be electrically coupled to an electrical nerve stimulation generator to provide electrical stimulation for electrically stimulating and locating the target nerve. In some aspects, the heater assembly includes a heater block. In some aspects, the heater electrode may advantageously provide a confirmation signal that the heater is in contact with the skin surface for patient safety purposes. For example, the confirmation may comprise an impedance measurement that is below 10 K ohms.

In yet other embodiments, a method of treating a nerve is provided that includes the steps of: inserting one or more needles of a needle assembly into a tissue of a patient, electrically stimulating the nerve with the needle assembly via bipolar electrical stimulation to localize the nerve within the tissue, and after localizing of the nerve via bipolar electrical stimulation, delivering cryoneurolysis to the nerve with the needle assembly.

In certain aspects, the method further includes electrically stimulating the nerve with the needle assembly via monopolar electrical stimulation prior to electrically stimulating the nerve with the needle assembly via bipolar electrical stimulation to initially localize the nerve within the tissue. For example, the method could employ a third electrical contact acting as a return (or anode) connection located on the skin surface of the skin. The device would then provide a stimulation signal between its active (or cathode) electrode in the needle assembly and the skin electrode to provide monopolar stimulation to allow the user to initially locate the target nerve for gross positioning. Following this, the user could then switch to a bipolar stimulation mode that would break the return connection with the skin electrode and provide a stimulation signal path between the active electrode and a second return electrode located on the same or adjacent needle. This bipolar stimulation would then be used to precisely locate and fine tune needle placement on the target nerve.

According to other aspects, the method further includes electrically stimulating the nerve with the needle assembly via bipolar electrical stimulation to localize the nerve within the tissue includes generating a first electric field about asymmetrically located first and second electrical contacts coupled to the needle assembly.

DESCRIPTION OF THE DRAWINGS

Further details, aspects and embodiments of the invention will be described by way of example only and with reference to the drawings. In the drawings, like reference numbers are used to identify like or functionally similar elements. Elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale.

FIG. 1A is a perspective view of a self-contained subdermal cryogenic probe and system, according to some embodiments of the invention;

FIG. 1B is a partially transparent perspective view of the self-contained probe of FIG. 1A, showing internal components of the cryogenic system and schematically illustrating replacement treatment needles for use with the disposable probe according to some embodiments of the invention;

FIG. 2A schematically illustrates exemplary components that may be included in the treatment system;

FIG. 2B is a cross-sectional view of the system of FIG. 1A, according to some embodiments of the invention;

FIGS. 2C and 2D are cross-sectional views showing exemplary operational configurations of a portion of the system of FIG. 2B;

FIGS. 3A-3E illustrate exemplary embodiments of needle probes, according to some embodiments of the invention;

FIGS. 4A and 4B illustrate an exemplary system according to some embodiments;

FIG. 5A illustrates an exemplary method of treating a nerve according to some embodiments;

FIG. 5B illustrates another exemplary method of locating and treating a nerve according to some embodiments;

FIG. 6A illustrates an exemplary needle assembly according to some embodiments;

FIG. 6B illustrates a close up view of a needle of the exemplary needle assembly of FIG. 6A according to some embodiments;

FIG. 6C illustrates an exemplary needle configuration according to some embodiments;

FIG. 7 illustrates an exemplary treatment system with a replaceable needle assembly having an electrical port for coupling with a waveform generator of a percutaneous electrical stimulation device according to some embodiments;

FIG. 8 illustrates the exemplary replaceable needle assembly of FIG. 7 according to some embodiments;

FIG. 9 illustrates yet another exemplary treatment system with a handle having an electrical port for coupling with a waveform generator of a percutaneous electrical nerve stimulation device according to some embodiments;

FIG. 10 illustrates a view of a proximal end of the exemplary treatment system of FIG. 9 according to some embodiments;

FIG. 11 illustrates yet another exemplary treatment system with a fully integrated percutaneous electrical stimulation device according to some embodiments;

FIG. 12 illustrates another exemplary needle assembly according to some embodiments;

FIG. 13 illustrates an exemplary treatment system with an integrated transcutaneous electrical nerve stimulation probe according to some embodiments;

FIG. 14 illustrates an exemplary operation of the exemplary system of FIG. 13 according to some embodiments;

FIG. 15A illustrates an exemplary needle assembly of an integrated cold therapy and electrical stimulation system according to some embodiments;

FIG. 15B illustrates another exemplary needle assembly of an integrated cold therapy and electrical stimulation system according to some embodiments;

FIGS. 16A-16D illustrate other exemplary needle assemblies of an integrated cold therapy and electrical stimulation system according to some embodiments;

FIGS. 17A-17C illustrate yet other exemplary needle assemblies of an integrated cold therapy and electrical stimulation system according to some embodiments; and

FIG. 18 illustrates an exemplary needle assembly of an integrated cold therapy and electrical stimulation system according to some embodiments.

DETAILED DESCRIPTION

The present invention provides improved medical devices, systems, and methods. Embodiments of the invention may treat target tissues disposed at and below the skin, optionally to treat pain associated with a sensory nerve. In some embodiments, systems, devices, and methods of the present disclosure may utilize an integrated cold therapy and nerve stimulation device for localization and treatment of a target nerve.

Embodiments of the invention may utilize a handheld refrigeration system that can use a commercially available cartridge of fluid refrigerant. Refrigerants well-suited for use in handheld refrigeration systems may include nitrous oxide and carbon dioxide. These can achieve temperatures approaching −90° C.

Sensory nerves and associated tissues may be temporarily impaired using moderately cold temperatures of 10° C. to −5° C. without permanently disabling the tissue structures. Using an approach similar to that employed for identifying structures associated with atrial fibrillation or for peripheral nerve blocks, a needle probe or other treatment device can be used to identify a target tissue structure in a diagnostic mode with these moderate temperatures, and the same probe (or a different probe) can also be used to provide a longer term or permanent treatment, optionally by treating the target tissue zone and/or inducing apoptosis at temperatures from about −5° C. to about −50° C. In some embodiments, apoptosis may be induced using treatment temperatures from about −1° C. to about −15° C., or from about −1° C. to about −19° C., optionally so as to provide a longer lasting treatment that limits or avoids inflammation and mobilization of skeletal muscle satellite repair cells. In some embodiments, axonotmesis with Wallerian degeneration of a sensory nerve is desired, which may be induced using treatment temperatures from about −20° C. to about −100° C. Hence, the duration of the treatment efficacy of such subdermal cryogenic treatments may be selected and controlled, with colder temperatures, longer treatment times, and/or larger volumes or selected patterns of target tissue determining the longevity of the treatment. Additional description of cryogenic cooling methods and devices may be found in commonly assigned U.S. Pat. No. 7,713,266 (Atty. Docket No. 000110US) entitled “Subdermal Cryogenic Remodeling of Muscle, Nerves, Connective Tissue, and/or Adipose Tissue (Fat)”, U.S. Pat. No. 7,850,683 (Atty. Docket No. 000120US) entitled “Subdermal Cryogenic Remodeling of Muscles, Nerves, Connective Tissue, and/or Adipose Tissue (Fat)”, U.S. Pat. No. 9,039,688 (Atty. Docket No. 002510US) entitled “Method for Reducing Hyperdynamic Facial Wrinkles”, and U.S. Pat. No. 8,298,216 (Atty. Docket No. 000810US) entitled “Pain Management Using Cryogenic Remodeling,” the full disclosures of which are each incorporated by reference herein.

Referring now to FIGS. 1A and 1B, a system for cryogenic remodeling here comprises a self-contained probe handpiece generally having a proximal end 12 and a distal end 14. A handpiece body or housing 16 has a size and ergonomic shape suitable for being grasped and supported in a surgeon's hand or other system operator. As can be seen most clearly in FIG. 1B, a cryogenic cooling fluid supply 18, a supply valve 32 and electrical power source 20 are found within housing 16, along with a circuit 22S having a processor for controlling cooling applied by self-contained system 10 in response to actuation of an input 24. Alternatively, electrical power can be applied through a cord from a remote power source. Power source 20 may also supply power to an optional heater element 44 in order to heat the proximal region of probe 26 which may thereby help to prevent unwanted skin damage, and a temperature sensor 48 adjacent the proximal region of probe 26 which helps monitor probe temperature. Additional details on the heater 44 and temperature sensor 48 are described in greater detail below. When actuated, supply valve 32 controls the flow of cryogenic cooling fluid from fluid supply 18. Some embodiments may, at least in part, be manually activated, such as through the use of a manual supply valve and/or the like, so that processors, electrical power supplies, and the like may not be required.

Extending distally from distal end 14 of housing 16 may be a tissue-penetrating cryogenic cooling probe 26. Probe 26 is thermally coupled to a cooling fluid path extending from cooling fluid source 18, with the exemplary probe comprising a tubular body receiving at least a portion of the cooling fluid from the cooling fluid source therein. The probe 26 may comprise a 30 G needle or smaller gauge (e.g., 27 G) having a sharpened distal end that is axially sealed. Probe 26 may have an axial length between distal end 14 of housing 16 and the distal end of the needle of between about 0.5 mm and 15 cm. Such needles may comprise a stainless steel tube with an inner diameter of about 0.006 inches and an outer diameter of about 0.012 inches, while alternative probes may comprise structures having outer diameters (or other lateral cross-sectional dimensions) from about 0.006 inches to about 0.100 inches. Generally, needle probe 26 may comprise a 16 G or smaller diameter needle, often comprising a 20 G needle or smaller, typically comprising a 22, 25, 26, 27, 28, 29, or 30 G or smaller diameter needle.

In some embodiments, probe 26 may comprise two or more needles arranged in a linear array, such as those disclosed in previously incorporated U.S. Pat. No. 7,850,683. Another exemplary embodiment of a probe having multiple needle probe configurations allow the cryogenic treatment to be applied to a larger or more specific treatment area. Other needle configurations that facilitate controlling the depth of needle penetration and insulated needle embodiments are disclosed in commonly assigned U.S. Pat. No. 8,409,185 (Atty. Docket No. 000500US) entitled “Replaceable and/or Easily Removable Needle Systems for Dermal and Transdermal Cryogenic Remodeling,” the entire content of which is incorporated herein by reference. Multiple needle arrays may also be arrayed in alternative configurations such as a triangular or square array.

Arrays may be designed to treat a particular region of tissue, or to provide a uniform treatment within a particular region, or both. In some embodiments needle 26 may be releasably coupled with body 16 so that it may be replaced after use with a sharper needle (as indicated by the dotted line) or with a needle having a different configuration. In exemplary embodiments, the needle may be threaded into the body, press fit into an aperture in the body or have a quick disconnect such as a detent mechanism for engaging the needle with the body. A quick disconnect with a check valve may be advantageous since it may permit decoupling of the needle from the body at any time without excessive coolant discharge. This can be a useful safety feature in the event that the device fails in operation (e.g. valve failure), allowing an operator to disengage the needle and device from a patient's tissue without exposing the patient to coolant as the system depressurizes. This feature may also be advantageous because it allows an operator to easily exchange a dull needle with a sharp needle in the middle of a treatment. One of skill in the art will appreciate that other coupling mechanisms may be used.

Addressing some of the components within housing 16, the exemplary cooling fluid supply 18 may comprise a canister, sometimes referred to herein as a cartridge, containing a liquid under pressure, with the liquid preferably having a boiling temperature of less than 37° C. at one atmosphere of pressure. When the fluid is thermally coupled to the tissue-penetrating probe 26, and the probe is positioned within the patient so that an outer surface of the probe is adjacent to a target tissue, the heat from the target tissue evaporates at least a portion of the liquid and the enthalpy of vaporization cools the target tissue. A supply valve 32 may be disposed along the cooling fluid flow path between canister 18 and probe 26, or along the cooling fluid path after the probe so as to limit coolant flow thereby regulating the temperature, treatment time, rate of temperature change, or other cooling characteristics. The valve will often be powered electrically via power source 20, per the direction of processor 22, but may at least in part be manually powered. The exemplary power source 20 comprises a rechargeable or single-use battery. Additional details about valve 32 are disclosed below and further disclosure on the power source 20 may be found in commonly assigned Int'l Pub. No. WO 2010/075438 (Atty. Docket No. 002310PC) entitled “Integrated Cryosurgical Probe Package with Fluid Reservoir and Limited Electrical Power Source,” the entire contents of which are incorporated herein by reference.

The exemplary cooling fluid supply 18 may comprise a single-use canister. Advantageously, the canister and cooling fluid therein may be stored and/or used at (or even above) room temperature. The canister may have a frangible seal or may be refillable, with the exemplary canister containing liquid nitrous oxide, N₂O. A variety of alternative cooling fluids might also be used, with exemplary cooling fluids including fluorocarbon refrigerants and/or carbon dioxide. The quantity of cooling fluid contained by canister 18 will typically be sufficient to treat at least a significant region of a patient, but will often be less than sufficient to treat two or more patients. An exemplary liquid N₂O canister might contain, for example, a quantity in a range from about 1 gram to about 40 grams of liquid, more preferably from about 1 gram to about 35 grams of liquid, and even more preferably from about 7 grams to about 30 grams of liquid.

Processor or controller 22 will typically comprise a programmable electronic microprocessor embodying machine readable computer code or programming instructions for implementing one or more of the treatment methods described herein. The microprocessor will typically include or be coupled to a memory (such as a non-volatile memory, a flash memory, a read-only memory (“ROM”), a random access memory (“RAM”), or the like) storing the computer code and data to be used thereby, and/or a recording media (including a solid state recording media such as a flash memory drive; a magnetic recording media such as a hard disk, a floppy disk, or the like; or an optical recording media such as a CD or DVD) may be provided. Suitable interface devices (such as digital-to-analog or analog-to-digital converters, or the like) and input/output devices (such as USB or serial I/O ports, wireless communication cards, graphical display cards, and the like) may also be provided. A wide variety of commercially available or specialized processor structures may be used in different embodiments, and suitable processors may make use of a wide variety of combinations of hardware and/or hardware/software combinations. For example, processor 22 may be integrated on a single processor board and may run a single program or may make use of a plurality of boards running a number of different program modules in a wide variety of alternative distributed data processing or code architectures.

Referring now to FIG. 2A, schematic 11 shows a simplified diagram of cryogenic cooling fluid flow and control. The flow of cryogenic cooling fluid from fluid supply 18 may be controlled by a supply valve 32. Supply valve 32 may comprise an electrically actuated solenoid valve, a motor actuated valve or the like operating in response to control signals from controller 22, and/or may comprise a manual valve. Exemplary supply valves may comprise structures suitable for on/off valve operation, and may provide venting of the fluid source and/or the cooling fluid path downstream of the valve when cooling flow is halted so as to limit residual cryogenic fluid vaporization and cooling. Additionally, the valve may be actuated by the controller in order to modulate coolant flow to provide high rates of cooling in some instances where it is desirable to promote necrosis of tissue such as in malignant lesions and the like or slow cooling which promotes ice formation between cells rather than within cells when necrosis is not desired. More complex flow modulating valve structures might also be used in other embodiments. For example, other applicable valve embodiments are disclosed in previously incorporated U.S. Pat. No. 8,409,185.

Still referring to FIG. 2A, an optional heater (not illustrated) may be used to heat cooling fluid supply 18 so that heated cooling fluid flows through valve 32 and through a lumen 34 of a cooling fluid supply tube 36. In some embodiments a safety mechanism can be included so that the cooling supply is not overheated. Examples of such embodiments are disclosed in commonly assigned International Publication No. WO 2010075438, the entirety of which is incorporated by reference herein.

Supply tube 36 is, at least in part, disposed within a lumen 38 of needle 26, with the supply tube extending distally from a proximal end 40 of the needle toward a distal end 42. The exemplary supply tube 36 comprises a fused silica tubular structure (not illustrated) having a polymer coating and extending in cantilever into the needle lumen 38. Supply tube 36 may have an inner lumen with an effective inner diameter of less than about 200 μm, the inner diameter often being less than about 100 μm, and typically being less than about 70 μm. Exemplary embodiments of supply tube 36 have inner lumens of between about 15 and 70 μm, such as about 30 μm or 65 μm. An outer diameter or size of supply tube 36 will typically be less than about 1000 μm, often being less than about 800 μm, with exemplary embodiments being between about 60 and 150 μm, such as about 90 μm or 105 μm. The tolerance of the inner lumen diameter of supply tubing 36 will preferably be relatively tight, typically being about +/−10 μm or tighter, often being +/−5 μm or tighter, and ideally being +/−3 μm or tighter (e.g., +/−1 μm), as the small diameter supply tube may provide the majority of (or even substantially all of) the metering of the cooling fluid flow into needle 26. Additional details on various aspects of needle 26 along with alternative embodiments and principles of operation are disclosed in greater detail in U.S. Pat. No. 9,254,162 (Atty. Docket No. 000300US) entitled “Dermal and Transdermal Cryogenic Microprobe Systems and Methods,” the entire contents of which are incorporated herein by reference. Previously incorporated U.S. Pat. No. 8,409,185 (Attorney Docket No. 000500US) also discloses additional details on the needle 26 along with various alternative embodiments and principles of operation.

The cooling fluid injected into lumen 38 of needle 26 will typically comprise liquid, though some gas may also be injected. At least some of the liquid vaporizes within needle 26, and the enthalpy of vaporization cools the needle and also the surrounding tissue engaged by the needle. An optional heater 44 (illustrated in FIG. 1B) may be used to heat the proximal region of the needle in order to prevent unwanted skin damage in this area, as discussed in greater detail below. Controlling a pressure of the gas/liquid mixture within needle 26 substantially controls the temperature within lumen 38, and hence the treatment temperature range of the tissue. A relatively simple mechanical pressure relief valve 46 may be used to control the pressure within the lumen of the needle, with the exemplary valve comprising a valve body such as a ball bearing, urged against a valve seat by a biasing spring. An exemplary relief valve is disclosed in U.S. Provisional Patent Application No. 61/116,050 previously incorporated herein by reference. Thus, the relief valve may allow better temperature control in the needle, minimizing transient temperatures. Further details on exhaust volume are disclosed in previously incorporated U.S. Pat. No. 8,409,185.

The heater 44 may be thermally coupled to a thermally responsive element 50, which is supplied with power by the controller 22 and thermally coupled to a proximal portion of the needle 26. The thermally responsive element 50 can be a block constructed from a material of high thermal conductivity and low heat capacity, such as aluminum. A first temperature sensor 52 (e.g., thermistor, resistance temperature detectors, or thermocouple) can also be thermally coupled the thermally responsive element 50 and communicatively coupled to the controller 22. A second temperature sensor 53 can also be positioned near the heater 44, for example, such that the first temperature sensor 52 and second temperature sensor 53 are placed in different positions within the thermally responsive element 50. In some embodiments, the second temperature sensor 53 is placed closer to a tissue contacting surface than the first temperature sensor 52 is placed in order to provide comparative data (e.g., temperature differential) between the sensors 52, 53. The controller 22 can be configured to receive temperature information of the thermally responsive element 50 via the temperature sensor 52 in order to provide the heater 44 with enough power to maintain the thermally responsive element 50 at a particular temperature.

The controller 22 can be further configured to monitor power draw from the heater 44 in order to characterize tissue type, perform device diagnostics, and/or provide feedback for a tissue treatment algorithm. This can be advantageous over monitoring temperature alone, since power draw from the heater 44 can vary greatly while temperature of the thermally responsive element 50 remains relatively stable. For example, during treatment of target tissue, maintaining the thermally responsive element 50 at 40° C. during a cooling cycle may take 1.0 W initially (for a needle <10 mm in length) and is normally expected to climb to 1.5 W after 20 seconds, due to the needle 26 drawing in surrounding heat. An indication that the heater is drawing 2.0 W after 20 seconds to maintain 40° C. can indicate that an aspect of the system 10 is malfunctioning and/or that the needle 26 is incorrectly positioned. Correlations with power draw and correlated device and/or tissue conditions can be determined experimentally to determine acceptable treatment power ranges.

In some embodiments, it may be preferable to limit frozen tissue that is not at the treatment temperature, i.e., to limit the size of a formed cooling zone within tissue. Such cooling zones may be associated with a particular physical reaction, such as the formation of an ice-ball, or with a particular temperature profile or temperature volume gradient required to therapeutically affect the tissue therein. To achieve this, metering coolant flow could maintain a large thermal gradient at its outside edges. This may be particularly advantageous in applications for creating an array of connected cooling zones (i.e., fence) in a treatment zone, as time would be provided for the treatment zone to fully develop within the fenced in portion of the tissue, while the outer boundaries maintained a relatively large thermal gradient due to the repeated application and removal of refrigeration power. This could provide a mechanism within the body of tissue to thermally regulate the treatment zone and could provide increased ability to modulate the treatment zone at a prescribed distance from the surface of the skin. A related treatment algorithm could be predefined, or it could be in response to feedback from the tissue.

Such feedback could be temperature measurements from the needle 26, or the temperature of the surface of the skin could be measured. However, in many cases monitoring temperature at the needle 26 is impractical due to size constraints. To overcome this, operating performance of the sensorless needle 26 can be interpolated by measuring characteristics of thermally-coupled elements, such as the thermally responsive element 50.

Additional methods of monitoring cooling and maintaining an unfrozen portion of the needle include the addition of a heating element and/or monitoring element into the needle itself. This could consist of a small thermistor or thermocouple, and a wire that could provide resistive heat. Other power sources could also be applied such as infrared light, radiofrequency heat, and ultrasound. These systems could also be applied together dependent upon the control of the treatment zone desired.

Alternative methods to inhibit excessively low transient temperatures at the beginning of a refrigeration cycle might be employed instead of or together with the limiting of the exhaust volume. For example, the supply valve 32 might be cycled on and off, typically by controller 22, with a timing sequence that would limit the cooling fluid flowing so that only vaporized gas reached the needle lumen 38 (or a sufficiently limited amount of liquid to avoid excessive dropping of the needle lumen temperature). This cycling might be ended once the exhaust volume pressure was sufficient so that the refrigeration temperature would be within desired limits during steady state flow. Analytical models that may be used to estimate cooling flows are described in greater detail in previously incorporated U.S. Pat. No. 9,254,162.

FIG. 2B shows a cross-section of the housing 16. This embodiment of the housing 16 may be powered by an external source, hence the attached cable, but could alternatively include a portable power source. As shown, the housing includes a cartridge holder 50. The cartridge holder 50 includes a cartridge receiver 52, which may be configured to hold a pressured refrigerant cartridge 18. The cartridge receiver 52 includes an elongated cylindrical passage 70, which is dimensioned to hold a commercially available cooling fluid cartridge 18. A distal portion of the cartridge receiver 52 includes a filter device 56, which has an elongated conical shape. In some embodiments, the cartridge holder 50 may be largely integrated into the housing 16 as shown, however, in alternative embodiments, the cartridge holder 50 is a wholly separate assembly, which may be pre-provided with a coolant fluid source 18.

The filter device 56 may fluidly couple the coolant fluid source (cartridge) 18 at a proximal end to the valve 32 at a distal end. The filter device 56 may include at least one particulate filter 58. In the shown embodiment, a particulate filter 58 at each proximal and distal end of the filter device 56 may be included. The particulate filter 58 can be configured to prevent particles of a certain size from passing through. For example, the particulate filter 58 can be constructed as a microscreen having a plurality of passages less than 2 microns in width, and thus particles greater than 2 microns would not be able to pass.

The filter device 56 also includes a molecular filter 60 that is configured to capture fluid impurities. In some embodiments, the molecular filter 60 is a plurality of filter media (e.g., pellets, powder, particles) configured to trap molecules of a certain size. For example, the filter media can comprise molecular sieves having pores ranging from 1-20 Å. In another example, the pores have an average size of 5 Å. The molecular filter 60 can have two modalities. In a first mode, the molecular filter 60 will filter fluid impurities received from the cartridge 18. However, in another mode, the molecular filter 60 can capture impurities within the valve 32 and fluid supply tube 36 when the system 10 is not in use, i.e., when the cartridge 18 is not fluidly connected to the valve 32.

Alternatively, the filter device 56 can be constructed primarily from ePTFE (such as a Gore-Tex® material), sintered polyethylene (such as made by POREX), or metal mesh. The pore size and filter thickness can be optimized to minimize pressure drop while capturing the majority of contaminants. These various materials can be treated to make it hydrophobic (e.g., by a plasma treatment) and/or oleophobic so as to repel water or hydrocarbon contaminants.

It has been found that in some instances fluid impurities may leach out from various aspects of the system 10. These impurities can include trapped moisture in the form of water molecules and chemical gasses. The presence of these impurities is believed to hamper cooling performance of the system 10. The filter device 56 can act as a desiccant that attracts and traps moisture within the system 10, as well as chemicals out gassed from various aspects of the system 10. Alternately the various aspects of the system 10 can be coated or plated with impermeable materials such as a metal.

As shown in FIG. 2B and in more detail in FIG. 2C and FIG. 2D, the cartridge 18 can be held by the cartridge receiver 52 such that the cartridge 18 remains intact and unpunctured. In this inactive mode, the cartridge may not be fluidly connected to the valve 32. A removable cartridge cover 62 can be attached to the cartridge receiver 52 such that the inactive mode is maintained while the cartridge is held by the system 10.

In use, the cartridge cover 62 can be removed and supplied with a cartridge containing a cooling fluid. The cartridge cover 62 can then be reattached to the cartridge receiver 52 by turning the cartridge cover 62 until female threads 64 of the cartridge cover 62 engage with male threads of the cartridge receiver 52. The cartridge cover 62 can be turned until resilient force is felt from an elastic seal 66, as shown in FIG. 2C. To place the system 10 into use, the cartridge cover 62 can be further turned until the distal tip of the cartridge 18 is punctured by a puncture pin connector 68, as shown in FIG. 2D. Once the cartridge 18 is punctured, cooling fluid may escape the cartridge by flowing through the filter device 56, where the impurities within the cooling fluid may be captured. The purified cooling fluid then passes to the valve 32, and onto the coolant supply tube 36 to cool the probe 26. In some embodiments the filter device, or portions thereof, may be replaceable.

In some embodiments, the puncture pin connector 68 can have a two-way valve (e.g., ball/seat and spring) that is closed unless connected to the cartridge. Alternately, pressure can be used to open the valve. The valve closes when the cartridge is removed. In some embodiments, there may be a relief valve piloted by a spring which is balanced by high-pressure nitrous when the cartridge is installed and the system is pressurized, but allows the high-pressure cryogen to vent when the cryogen is removed. In addition, the design can include a vent port that vents cold cryogen away from the cartridge port. Cold venting cryogen locally can cause condensation in the form of liquid water to form from the surrounding environment. Liquid water or water vapor entering the system can hamper the cryogenic performance. Further, fluid carrying portions of the cartridge receiver 52 can be treated (e.g., plasma treatment) to become hydrophobic and/or oleophobic so as to repel water or hydrocarbon contaminants.

Turning now to FIG. 3A and FIG. 3B, an exemplary embodiment of probe 300 having multiple needles 302 is described. In FIG. 3A, probe housing 316 includes threads 306 that allow the probe to be threadably engaged with the housing 16 of a cryogenic device. O-rings 308 fluidly seal the probe housing 316 with the device housing 16 and prevent coolant from leaking around the interface between the two components. Probe 300 includes an array of three distally extending needle shafts 302, each having a sharpened, tissue penetrating tip 304. In certain embodiments, using three linearly arranged needles allows a greater area of tissue to be treated as compared with a single needle. In use, coolant flows through lumens 310 into the needle shafts 302 thereby cooling the needle shafts 302. Ideally, only the distal portion of the needle shaft 302 would be cooled so that only the target tissue receives the cryogenic treatment. However, as the cooling fluid flows through the probe 300, probe temperature decreases proximally along the length of the needle shafts 302 towards the probe hub 318. The proximal portion of needle shaft 302 and the probe hub 318 contact skin and may become very cold (e.g. −20° C. to −25° C.) and this can damage the skin in the form of blistering or loss of skin pigmentation. Therefore it would be desirable to ensure that the proximal portion of needle shaft 302 and hub 318 remains warmer than the distal portion of needle shaft 302. A proposed solution to this challenge is to include a heater element 314 that can heat the proximal portion of needle shaft 302 and an optional temperature sensor 312 to monitor temperature in this region. To further this, a proximal portion of the needle shaft 302 can be coated with a highly thermally conductive material, e.g., gold, that is conductively coupled to both the needle shaft 302 and heater element 314. Details of this construction are disclosed below.

In the exemplary embodiment of FIG. 3A, heater element 314 is disposed near the needle hub 318 and near a proximal region of needle shaft 302. The effective resistance of the heater element is preferably 1Ω to 1K Ω, and more preferably from 3Ω to 50Ω. Additionally, a temperature sensor 312 such as a thermistor or thermocouple is also disposed in the same vicinity. Thus, during a treatment as the needles cool down, the heater 314 may be turned on in order to heat the hub 318 and proximal region of needle shaft 302, thereby preventing this portion of the device from cooling down as much as the remainder of the needle shaft 302. The temperature sensor 312 may provide feedback to controller 22 and a feedback loop can be used to control the heater 314. The cooling power of the nitrous oxide may eventually overcome the effects of the heater, therefore the microprocessor may also be programmed with a warning light and/or an automatic shutoff time to stop the cooling treatment before skin damage occurs. An added benefit of using such a heater element is the fact that the heat helps to moderate the flow of cooling fluid into the needle shaft 302 helping to provide more uniform coolant mass flow to the needles shaft 302 with more uniform cooling resulting.

The embodiment of FIG. 3A illustrates a heater fixed to the probe hub. In other embodiments, the heater may float, thereby ensuring proper skin contact and proper heat transfer to the skin. Examples of floating heaters are disclosed in commonly assigned Int'l Pub. No. WO 2010/075448 (Atty. Docket No. 002310PC) entitled “Skin Protection for Subdermal Cryogenic Remodeling for Cosmetic and Other Treatments,” the entirety of which is incorporated by reference herein.

In this exemplary embodiment, three needles are illustrated. One of skill in the art will appreciate that a single needle may be used, as well as two, four, five, six, or more needles may be used. When a plurality of needles are used, they may be arranged in any number of patterns. For example, a single linear array may be used, or a two dimensional or three dimensional array may be used. Examples of two dimensional arrays include any number of rows and columns of needles (e.g. a rectangular array, a square array, elliptical, circular, triangular, etc.), and examples of three dimensional arrays include those where the needle tips are at different distances from the probe hub, such as in an inverted pyramid shape.

FIG. 3B illustrates a cross-section of the needle shaft 302 of needle probe 300. The needle shaft can be conductively coupled (e.g., welded, conductively bonded, press fit) to a conductive heater 314 to enable heat transfer therebetween. The needle shaft 302 is generally a small (e.g., 20-30 gauge) closed tip hollow needle, which can be between about 0.2 mm and 15 cm, preferably having a length from about 0.3 cm to about 10 cm. The conductive heater element 314 can be housed within a conductive block 315 of high thermally conductive material, such as aluminum and include an electrically insulated coating, such as Type III anodized coating to electrically insulate it without diminishing its heat transfer properties. The conductive block 315 can be heated by a resistor or other heating element (e.g. cartridge heater, nichrome wire, semiconductor device, etc.) bonded thereto with a heat conductive adhesive, such as epoxy. A thermistor can be coupled to the conductive block 315 with heat-conductive epoxy or other thermally conductive means to allow for temperature monitoring. Other temperature sensors may also be used, such as a thermocouple or resistance temperature detectors.

An optional cladding 320 of conductive material may be conductively coupled to the proximal portion of the shaft of the needle 302, which can be stainless steel. In some embodiments, the cladding 320 is a layer of gold, or alloys thereof, coated on the exterior of the proximal portion of the needle shaft 302. In some embodiments, the exposed length of cladding 320 on the proximal portion of the needle is 2-100 mm. In some embodiments, the cladding 320 can be of a thickness such that the clad portion has a diameter ranging from 0.017-0.020 in., and in some embodiments 0.0182 in. Accordingly, the cladding 320 can be conductively coupled to the material of the needle 302, which can be less conductive, than the cladding 320. The cladding 320 may modify the lateral force required to deflect or bend the needle 26. Cladding 320 may be used to provide a stiffer needle shaft along the proximal end in order to more easily transfer force to the leading tip during placement and allow the distal portion of the needle to deflect more easily when it is dissecting a tissue interface within the body. The stiffness of needle 26 can vary from one end to the other end by other means such as material selection, metal tempering, variation of the inner diameter of the needle 26, or segments of needle shaft joined together end-to-end to form one contiguous needle 26. In some embodiments, increasing the stiffness of the distal portion of the needle 26 can be used to flex the proximal portion of the needle to access difficult treatment sites as in the case of upper limb spasticity where bending of the needle outside the body may be used to access a target peripheral nerve along the desired tissue plane.

In some embodiments, the cladding 320 can include sub-coatings (e.g., nickel) that promote adhesion of an outer coating that would otherwise not bond well to the needle shaft 302. Other highly conductive materials can be used as well, such as copper, silver, aluminum, and alloys thereof. In some embodiments, a protective polymer or metal coating can cover the cladding to promote biocompatibility of an otherwise non-biocompatible but highly conductive cladding material. Such a biocompatible coating however, would be applied to not disrupt conductivity between the conductive block 315. In some embodiments, an insulating layer, such as a ceramic material, is coated over the cladding 320, which remains conductively coupled to the needle shaft 302.

In use, the cladding 320 can transfer heat to the proximal portion of the needle 302 to prevent directly surrounding tissue from dropping to cryogenic temperatures. Protection can be derived from heating the non-targeting tissue during a cooling procedure, and in some embodiments before the procedure as well. The mechanism of protection may be providing heat to pressurized cryogenic cooling fluid passing within the proximal portion of the needle to affect complete vaporization of the fluid. Thus, the non-target tissue in contact with the proximal portion of the needle shaft 302 does not need to supply heat, as opposed to target tissue in contact with the distal region of the needle shaft 302. To help further this effect, in some embodiments the cladding 320 is coating within the interior of the distal portion of the needle, with or without an exterior cladding. To additionally help further this effect, in some embodiments, the distal portion of the needle can be thermally isolated from the proximal portion by a junction, such as a ceramic junction. While in some further embodiments, the entirety of the proximal portion is constructed from a more conductive material than the distal portion.

In use, it has been determined experimentally that the cladding 320 can help limit formation of a cooling zone to the distal portion of the needle shaft 302, which tends to demarcate at a distal end of the cladding 320. Accordingly, cooling zones are formed only about the distal portions of the needles. Thus, non-target tissue in direct contact with proximal needle shafts remain protected from effects of cryogenic temperatures. Such effects can include discoloration and blistering of the skin. Such cooling zones may be associated with a particular physical reaction, such as the formation of an ice-ball, or with a particular temperature required to therapeutically affect the tissue therein.

Standard stainless steel needles and gold clad steel needles were tested in porcine muscle and fat. Temperatures were recorded measured 2 mm from the proximal end of the needle shafts, about where the cladding distally terminates, and at the distal tip of the needles. Temperatures for clad needles were dramatically warmer at the 2 mm point versus the unclad needles, and did not drop below 4° C. The 2 mm points of the standard stainless steel needles almost equalize in temperature with the distal tip at temperatures below 0° C.

FIGS. 3C and 3D illustrates a detachable probe tip 322 having a hub connector 324 and an elongated probe 326. The probe tip 322 shares much of its construction with probe 300. However, the elongated probe 326 features a blunt tip 328 that is adapted for blunt dissection of tissue. The blunt tip 328 can feature a full radius tip, less than a full radius tip, or conical tip. In some embodiments, a dulled or truncated needle is used. The elongated probe 326 can be 20 gauge or smaller in diameter, and in some embodiments range in size from 25-30 gauge. As with the embodiments described above, an internal supply tube 330 extends in cantilever. However, the exit of the supply tube 330 can be disposed at positions within the elongated probe 326 other than proximate the blunt tip 328. Further, the supply tube 330 can be adapted to create an elongated zone of cooling, e.g., by having multiple exit points for cryofluid to exit from.

The elongated probe 326 and supply tube 330 may be configured to resiliently bend in use, throughout their length at angles approaching 120°, with a 5-10 mm bend radius. This may be very challenging considering the small sizes of the elongated probe 326 and supply tube 330, and also considering that the supply tube 330 is often constructed from fused silica. Accordingly, the elongated probe 326 can be constructed from a resilient material, such as stainless steel, and of a particular diameter and wall thickness [0.004 to 1.0 mm], such that the elongated probe in combination with the supply tube 330 is not overly resilient so as to overtly resist manipulation, but sufficiently strong so as to prevent kinking that can result in coolant escaping. For example, the elongated probe can be 15 gauge or smaller in diameter, even ranging from 20-30 gauge in diameter. The elongated probe can have a very disparate length to diameter ratio, for example, the elongated probe can be greater than 30 mm in length, and in some cases range from 30-150 mm in length (e.g., 90 mm length). To further the aforementioned goals, the supply tube 330 can include a polymer coating 332, such as a polyimide coating that terminates approximately halfway down its length, to resist kinking and aid in resiliency. The polymer coating 332 can be a secondary coating over a primary polyimide coating that extends fully along the supply tube. However, it should be understood that the coating is not limited to polyimide, and other suitable materials can be used. In some embodiments, the flexibility of the elongated probe 326 will vary from the proximal end to the distal end. For example, by creating certain portions that have more or less flexibility than others. This may be done, for example, by modifying wall thickness, adding material (such as the cladding discussed above), and/or heat treating certain portions of the elongated probe 326 and/or supply tube 330. For example, decreasing the flexibility of elongated probe 326 along the proximal end can improve the transfer of force from the hand piece to the elongated probe end for better feel and easier tip placement for treatment. The elongated probe and supply line 330 are may be configured to resiliently bend in use to different degrees along the length at angles approaching 120°, with a varying bend radius as small as 5 mm. In some embodiments, the elongated probe 326 will have external markings along the needle shaft indicating the length of needle inserted into the tissue.

FIG. 3E illustrates an exemplary detachable probe tip 322 inserted through skin surface SS. As illustrated, the probe tip 322 is inserted along an insertion axis IA through the skin surface SS. Thereafter, the needle may be bent away from the insertion axis IA and advanced toward a target tissue TT in order to position blunt tip 328 adjacent to the target tissue TT. In some embodiments, the target tissue may be the infrapatellar branch of the saphenous nerve. In other embodiments the target tissue may be one or more branches of the anterior femoral cutaneous nerve or the lateral femoral cutaneous nerve.

In some embodiments, the probe tip 322 does not include a heating element, such as the heater described with reference to probe 300, since the effective treating portion of the elongated probe 326 (i.e., the area of the elongated probe where a cooling zone emanates from) is well laterally displaced from the hub connector 324 and elongated probe proximal junction. Embodiments of the supply tube are further described below and within commonly assigned U.S. Pub. No. 2012/0089211, which is incorporated by reference.

FIGS. 4A-4B illustrate a distal end of an exemplary cryoprobe 800 for treating a nerve according to some embodiments. The probe 800 may have a needle 805 extending distally that is configured to generate a cryozone (defined by the 0° C. isotherm) 810. In some embodiments, as illustrated in the close up of needle 805 in FIG. 4B, the needle 805 may include one or more marks along the length of the needle. The one or more marks may comprise a mark 815 for marking a distal end of the cryozone 810 that is generated by the probe 800, a mark 820 for marking a proximal end of the cryozone 810 that is generated by the probe 800, and/or a mark 825 for marking a center of a the cryozone 810 that is generated by the probe 800.

The marks 815, 820, 825 may be utilized for visually aligning the needle 805 of a probe 800 with a target nerve. For example, FIG. 5A illustrates an exemplary method 900 of treating a nerve according to some embodiments. At step 902, a needle of the cryotherapy probe is positioned across the target nerve. The one or more markings indicative of a treatment area (e.g., marks 815, 820, 825) of the needle may be aligned with the nerve 904. After alignment, the cryotherapy probe may be activated to deliver the cooling therapy 906.

In some embodiments, the needle may be provided with an echogenic coating that makes the needle more visible under ultrasound imaging. For example, in some embodiments, the entire length of the needle may be provided with an echogenic coating. Alternatively, the one or more of the marks 815, 820, 825, may be provided with an echogenic coating such that the distal end, proximal end, or center of the cryozone associated with the needle is visible under ultrasound imaging. In other embodiments, the one or more marks may be provided by a lack of echogenic coating. For example, in some embodiments, the length of the needle may be provided with an echogenic coating except for at the one or more marks 815, 820, 825, such that when viewed under ultrasound guidance, the distal, proximal, or center of the cryozone would be associated with the portion of the needle without the echogenic coating. Alternatively, the length of the needle may be provided with the echogenic coating that ceases at the center of the associated cryozone, such that when viewed under ultrasound guidance, the distal end of the echogenic coating would be associated with a center of a cryozone of the needle.

Long needles may be used in some embodiments (e.g., 8-15 mm, 20 mm, 90 mm etc.). Longer needles may require a smaller gauge (larger diameter) needle so they have sufficient rigidity for improved control while positioning of the distal end deep in the tissue, but not so large as to create significant mechanical injury to the skin and tissue when inserted (e.g., greater diameter than 20 G). Alternate configurations of the device may have two or more needles spaced generally 2-5 mm apart of lengths ranging from up to 20 mm or greater, typically of 27 gauge, 25 gauge or 23 gauge. Single needle configurations may be even longer (e.g., 90 mm) for reaching target tissues that are even deeper (e.g., >15 mm or so below the dermis). Longer needle devices (e.g., >10 mm) may not need active heating of the skin warmer and/or cladding found in designs using shorter needle(s), as the cooling zone may be placed sufficiently deep below the dermis to prevent injury. In some embodiments, devices with single long needle configurations may benefit from active nerve location such as ultrasound or electrical nerve stimulation to guide placement of the needle. Further, larger targets may require treatment from both sides to make sure that the cold zone created by the needle fully covers the target. Adjacent treatments placing the needle to either side of a nerve during two successive treatment cycles may still provide an effective treatment of the entire nerve cross-section.

In some situations, a probe with multiple spaced apart needles may be preferable (e.g., 2, 3, 4 or more). A device employing multiple needles may decrease the total treatment duration by creating larger cooling zones. Further, a multi-needle device may be configured to provide continuous cooling zones between the spaced apart needles. In some embodiments, the needles may be spaced apart by 1-5 mm. The spacing may be dependent on the type of tissue being targeted. For example, when targeting a nerve, it may be preferable to position the nerve between the two or more needles so that cooling zones are generated on both sides of the nerve. Treating the nerve from both sides may increase the probability that the entire cross-section of the nerve will be treated. For superficial peripheral nerves, the nerves may be at depths ranging from 2-6 mm and may be smaller in diameter, typically <2 mm. Accordingly, devices for treating superficial peripheral nerves may comprise two or more 27 gauge needles spaced ≤2 mm apart and having typical lengths less than 7 mm (e.g., 6.9 mm); however longer needles may be required to treat the full patient population in order to access patients with altered nerve anatomy or patients with higher amounts of subcutaneous tissue such as those with high BMIs.

A treatment cycle may comprise a 10 second pre-warm phase, followed by a 60 second cooling phase, followed thereafter by a 15 second post-warm phase with 40° C. skin warmer throughout. It should be understood that other treatment cycles may be implemented. In some embodiments, a pre-warming cycle can range from 0 to up to 30 seconds, preferably 5-15 seconds sufficient to pre-warm the cryoprobe and opposing skin. Treatment cooling may range from 5-120 seconds, preferably 15-60 seconds based on the flow rate, geometry of the cryoprobe, size of the therapy zone, size of the target nerve or tissue and the mechanism of action desired. Post-warming can range from 0-120 seconds, preferably less than 60 seconds, more preferably 10-15 seconds sufficient to return the cryoprobe to a steady state thermal condition and possibly to free the cryoprobe needle(s) from the frozen therapy zone (e.g., at least 0° C.) prior to removing the cryoprobe needles. For example, in some embodiments, devices with 6.9 mm long cladded needles may be warmed with a 30° C. heater. The treatment cycle may comprise a 10 second pre-warm phase, a 35 second cooling phase, and a 15 second post-warm phase. Advantageously, such a treatment cycle may make an equivalent cryozone as the treatment cycle used in the study in a shorter amount of time (e.g., a 35 second cooling phase compared to a 60 second cooling phase).

In some embodiments, treatment devices and treatment cycles may be configured to deliver a preferred cryozone volume. For example, in some embodiments, devices and treatment cycles may be configured to generate cryozones having a cross-sectional area of approximately 14-55 mm2 (e.g., 27 mm2). Optionally, the devices and treatment cycles may be configured to generate cryozones having a volume of approximately 65-125 mm3 (e.g., 85 mm3).

Accordingly, in some embodiments, treatment cycles may be configured with cooling phases ranging between 15-75 seconds (e.g., 30 seconds, 35 seconds, 40 seconds, 45 seconds, etc.) depending on cooling fluid flow rates, warming phase durations, warming phase temperature, number of cooling needles, needle spacing, or the like in order to generate a desired cryozone. Similarly, treatment cycles may be configured with warming phases operating a temperatures ranging between 10-45° C. depending on the length of cooling phases, number of needles, needle spacing, etc., in order to generate a desired cryozone. In some embodiments the temperature can be set to one temperature during the pre-warm phase, another temperature during the cooling phase, and a third temperature during the post-warm phase.

In some embodiments, devices may be configured to limit flow rate of a cooling fluid to approximately 0.25-2.0 SLPM, preferably 0.34-1.0 SLPM (gas phase). Optionally, in some embodiments, it may be preferable to configure the device and the treatment cycle to maintain the tip at less than −55° C. during cooling phases. In some embodiments, it may be preferable to configure the device and the treatment cycle to have the tip return to at least 0° C. at the end of the post-warm phase so as to ensure the device may be safely removed from the tissue after the treatment cycle.

While generally describing treatment cycles as including pre-heating/warming phases, it should be understood that other treatment cycles may not require a pre-heating/warming phase. For example, larger needle devices (e.g., 30-90 mm) may not require a pre-heat/warm phase. Larger needles may rely on the body's natural heat to bring the needle to a desired temperature prior to a cooling phase.

In some embodiments of the present invention, treatment guidance can rely on rigid or boney landmarks because they are less dependent upon natural variations in body size or type, e.g. BMI. Soft tissues, vasculature and peripheral nerves pass adjacent to the rigid landmarks because they require protection and support. The target nerve to relieve pain can be identified based on the diagnosis along with patients identifying the area of pain, biomechanical movements that evoke pain from specific areas, palpation, and diagnostic nerve blocks using a temporary analgesic (e.g. 1-2% Lidocaine). Target nerve (tissue) can be located by relying on anatomical landmarks to indicate the anatomical area through which the target nerve (tissue) reside. Alternatively, nerve or tissue locating technologies can be used. In the case of peripheral nerves, electrical stimulation or ultrasound can be used to locate target nerves for treatment. Electrical nerve stimulation can identify the nerve upon stimulation and either innervated muscle twitch in the case of a motor nerve or altered sensation in a specific area in the case of a sensory nerve. Ultrasound is used to visualize the nerve and structures closely associated with the nerve (e.g. vessels) to assist in placing the cryoprobe in close proximity to the target nerve. By positioning the patient's skeletal structure in a predetermined position (e.g. knee bent 30 degrees or fully extended), one can reliably position the bones, ligaments, cartilage, muscle, soft tissues (including fascia), vasculature, and peripheral nerves. External palpation can then be used to locate the skeletal structure and thereby locate the pathway and relative depth of a peripheral nerve targeted for treatment.

A treatment of peripheral nerve tissue to at least −20° C. for greater than 10 seconds (e.g., at least 20 seconds preferably) may be sufficient to trigger 2nd degree Wallerian degeneration of the axon and myelinated sheath. Conduction along the nerve fibers is stopped immediately following treatment. This provides immediate feedback as to the location of the target peripheral nerve or associated branches when the associated motion or sensation is modified. This can be used to refine rigid landmark guidance of future treatments or to determine whether addition treatment is warranted.

By using rigid landmarks, one may be able to direct the treatment pattern to specific anatomical sites where the peripheral nerve is located with the highest likelihood. Feedback from the patient immediately after each treatment may verify the location of the target peripheral nerve and its associated branches. Thus, it should be understood that in some embodiments, the use of an electrical nerve stimulation device to discover nerve location is not needed or used, since well-developed treatment zones can locate target nerves. This may be advantageous, due the cost and complexity of electrical nerve stimulation devices, which are also not always readily available.

In alternative embodiments of the invention, one could use an electrical nerve stimulation device (either transcutaneous or percutaneous) to stimulate the target peripheral nerve and its branches. With transcutaneous electrical nerve stimulation (TENS), the pathway of the nerve branch can be mapped in XY-coordinates coincident with the skin surface. The Z-coordinate corresponding to depth normal to the skin surface can be inferred by the sensitivity setting of the electrical stimulation unit. For example, a setting of 3.25 mA and pulse duration of 0.1 ms may reliably stimulate the frontal branch of the temporal nerve when it is within 7 mm of the skin surface. If a higher current setting or longer pulse duration is required to stimulate the nerve, then the depth may be >7 mm. A percutaneous electrical nerve stimulator (PENS) can also be used to locate a target peripheral nerve. Based on rigid anatomical landmarks, a PENS needle can be introduced through the dermis and advanced into the soft tissues. Periodic stimulating pulses at a rate of 1-3 Hz may be used to stimulate nerves within a known distance from the PENS needle. When the target nerve is stimulated, the sensitivity of the PENS can be reduced (e.g., lowering the current setting or pulse duration), narrowing the range of stimulation. When the nerve is stimulated again, now within a smaller distance, the PENS sensitivity can be reduced further until the nerve stimulation distance is within the therapy zone dimensions. At this point, the PENS needle can be replaced with the cryoneurolysis needle(s) and a treatment can be delivered. The PENS and cryoneurolysis needles can be introduced by themselves or through a second larger gage needle or cannula. This may provide a rigid and reproducible path when introducing a needle and when replacing one needle instrument with another. A rigid pathway may guide the needle to the same location by preventing needle tip deflection, which could lead to a misplaced therapy and lack of efficacy.

While many of the examples disclosed herein relate to puncturing the skin in a transverse manner to arrive at a target nerve, other techniques can be used to guide a device to a target nerve. For example, insertion of devices can be made parallel to the surface of the skin, such that the (blunted) tip of the device glides along a particular fascia to arrive at a target sensory nerve. Such techniques and devices are disclosed in U.S. Pub. No. 2012/0089211, the entirety of which is incorporated by reference. Possible advantages may include a single insertion site and guidance of a blunt tip along a layer common with the path or depth of the target nerve. This technique may be a position-treatment-thaw, reposition-treatment-thaw, etc.

In further aspects of the present invention, a cryoneurolysis treatment device may be provided that is adapted to couple with or be fully integrated with a nerve stimulation device such that nerve stimulation and cryoneurolysis may be performed concurrently with the cryo-stimulation device. Accordingly, embodiments of the present disclosure may improve nerve targeting during cryoneurolysis procedures. Improvements in nerve localization and targeting may increase treatment accuracy and physician confidence in needle placement during treatment. In turn, such improvements may decrease overall treatment times, the number of repeat treatments, and the re-treatment rate. Further, additional improvements in nerve localization and targeting may reduce the number of applied treatment cycles and may also reduce the number of cartridge changes (when replaceable refrigerant cartridges are used). Thus, embodiments of the present disclosure may provide one or more advantages for cryoneurolysis by improving localization and treatment of target nerves. Hence, some aspects of the present disclosure provide methods, devices, and systems for localizing and targeting a nerve during cryoneurolysis procedures.

FIG. 5B illustrates one such method 500 of locating and treating a nerve according to some embodiments. At step 502, a transcutaneous electrical stimulation (TENS) device and/or anatomical landmarks may be used to pre-locate a target nerve or otherwise generally locate a target nerve location. At step 504, one or more needles of an integrated cooling and stimulation device may be inserted into the tissue. At step 506, percutaneous nerve localization may be conducted to determine 507 whether the one or more needles is proximal to the target nerve. If the nerve localization using percutaneous nerve stimulation 506 is unsuccessful, the one or more needles may be repositioned 508 within the tissue. Thereafter, percutaneous nerve localization 506 may be conducted again to determine whether the repositioning successfully places the one or more needles sufficiently proximal to the target nerve. If the nerve localization using percutaneous nerve stimulation is successful upon insertion 504 or after repositioning 508, cryoneurolysis may then be delivered 509 using one or more needles of the treatment device.

The method 500 may be used for cosmetic and/or other medical treatments (e.g., pain alleviation or the like). In some cosmetic applications, a target nerve may be between 3-7 mm in depth, for example. In other medical applications, a target nerve may be upwards of 50 mm in depth or deeper. It may be beneficial to locate the target nerve to within 2 mm for at least some of treatments. Additionally, in some applications, it may be beneficial to be able to locate and differentiate motor nerves from sensory nerves. For example, in some cosmetic applications that target motor nerves for wrinkle alleviation, it may be advantageous to locate and avoid treating sensory nerves to limit side effects due to the cosmetic procedure. For example, method 500 may be used to target the temporal branch of the facial nerve (TBFN). Additional nerves treated with method 500 in and around the face may include the auriculotemporal nerve. The nerves may run above the SDTF layer. The depth of the SDTF layer varies along treatment lines and among individuals and as such the target nerve depth may also vary from patient to patient. Accordingly, an integrated stimulation and cooling treatment device may be beneficial in such a procedure. In an additional non-limiting example, method 500 may be used to target the infrapatellar branch of the saphenous nerve (ISN). The ISN is a sensory nerve that innervates the anterior aspect of the knee. Cryoneurolysis of the ISN may alleviate pain experienced in the knee of a patient (e.g., due to osteoarthritis or the like). While anatomical features may be used to generally localize a treatment box for the target nerve, a plurality of treatments may be needed before the target nerve is treated within the box. Accordingly, an integrated nerve stimulation and cooling treatment device may provide more accurate treatments and may thereby limit the number of treatments required for treatment and reduce a treatment time. Additional treatments that may benefit from such a device include, but are not limited to: head pain, knee pain, plantar fasciitis, back pain, tendonitis, shoulder pain, movement disorders, intercostal pain, pre-surgical pain, post-herpetic neuralgia, post-surgical pain, phantom limb pain, etc. Associated nerves include: greater occipital nerve, lesser occipital nerve, trigeminal nerves, suprascapular nerve, intercostal nerves, brachialis nerve, superficial radial nerve, ilioinguinal nerve, iliohypogastric nerve, anterior femoral cutaneous nerve, lateral femoral cutaneous nerve, infrapatellar branch of the saphenous nerve, common peroneal nerve branches, tibial nerve branches, superficial peroneal nerve, sural nerve.

Electrical nerve stimulation localizes nerves by transmission of electrical pulses. The electrical impulses in turn excite nerves by inducing a flow of ions through the neuronal cell membrane (depolarization), which results in an action potential that may propagate bi-directionally. The nerve membrane depolarization may result in either muscle contraction or paresthesia, depending on the type of nerve fiber (motor vs. sensory). The current density a nerve reacts to or “sees” decreases with distance from the nerve:

$I = {k\left( \frac{i}{r^{2}} \right)}$

where k is a constant that depends on electrode size, pulse width, tissue impedance, nerve fiber size, etc.; i is the current delivered; and r is the distance from the nerve. This corresponds to higher threshold currents at a distance from the nerve.

In some embodiments, an insulated needle having a small conducting or uninsulated portion may have minimal current threshold when the needle is on the nerve. Non-insulated needles in contrast may transmit current through the entire length and may have a lower current density along the treatment portion of the needle. As such, non-insulated needles may require more current than insulated needles at the same distance from the nerve and may have less discrimination of distances as the needle approaches the nerve. Accordingly, while not essential, in some embodiments, cryo-stimulation devices may be provided that include an insulated nerve stimulation needle.

In some embodiments, the integrated cooling and stimulation needle probe may have a single needle for both cooling and nerve stimulation. For example, FIG. 6A illustrates an exemplary needle assembly 510 having a single needle 512 that may be used to perform the method 500 according to some embodiments of the disclosure. FIG. 6B illustrates a close up view of the needle 512 of the exemplary needle assembly 510 of FIG. 6A according to some embodiments. In use, coolant may flow through the needle 512 (e.g. via cooling fluid supply tube or the like) thereby cooling a distal end of the needle 512 and producing a cold zone 521 associated with the needle 512. The needle 512 may have a cooling center 522 along the length of the needle 512 that is associated with a center of the cold zone 521 produced by the needle 512. Additionally, the needle 512 may be constructed from an electrically conductive material and may also have an electrically insulated coating 523 disposed about a length of the needle 512. The electrically insulated coating 523 may electrically insulate a proximal portion of a length of the needle 512 that is adjacent the distal end of the housing 514 and may extend toward a distal portion of the length of the needle 512. The electrically insulated coating 523 may be a fluoropolymer coating, a silicone rubber coating, a parylene coating, a ceramic coating, an epoxy coating, a polyimide coating, or the like. A proximal end of needle 512 may be uninsulated and may be configured to couple with an electrical nerve stimulation generator 524 of a percutaneous electrical stimulation device. A distal end of needle 512 may be uninsulated such that an electric field 526 (FIG. 6B) generated by electrical nerve stimulation generator 524 happens about the distal end of needle 512. In some embodiments, the distal end of the electrically insulated coating 523 may be at the cooling center 522 of the needle 512. In such embodiments, the intensity of the electric field 526 produced by electrical nerve stimulation generator 524 may be co-incident with the center of the cold zone 521 that is produced by the needle 512, as illustrated in FIG. 6B.

In some embodiments the coating 523 may be 0.001 inches thick. Optionally, coating 523 may be applied by masking off the cooling center 522 of needle 512 and then coating the needle 512 with the electrically insulating material 523. Additionally, while needle assembly 510 is illustrated with a needle 512 without insulation at the distal end of the needle 512, it should be understood that this is exemplary. In some embodiments of the present disclosure, the distal end of needle 512 may have a coating of the electrically insulating material 523, as illustrated in FIG. 6C, while the portion of the needle 512 associated with the center of the cold zone 521 remains uninsulated.

As mentioned above, a proximal end of needle 512 may be uninsulated and may be configured to couple with an electrical nerve stimulation generator 524. In some embodiments, the electrical nerve stimulation generator 524 may have an input that is configured to couple with a corresponding electrical port of the treatment device. For example, FIG. 7 illustrates an exemplary treatment device 600. The treatment device 600 includes a handle 610 that is configured to be coupled with a replaceable needle assembly 612. The handle 610 may further include a replaceable refrigerant cartridge 614. The cartridge 614 may be secured to handle 610 by a cartridge cap 616. The cartridge 614 and the cartridge cap 616 may be housed by distal cover 618. Optionally, a needle assembly cover 620 may be provided to house the needle assembly 612 when the device 600 is not in use.

In some embodiments, the input electrical port configured to receive an input from the electrical nerve stimulation generator 524 may be provided on the replaceable needle assembly 612. For example, as illustrated in FIG. 8 illustrates an exemplary needle assembly 612 with an input electrical port 622. The input electrical port 622 is configured to couple with electrical nerve stimulation generator 524 to electrically couple the electrical nerve stimulation generator 524 with the uninsulated proximal portion of one or more electrical stimulation needles 623 of device 600.

Additionally, in some embodiments, the input electrical port configured to receive an input from the electrical nerve stimulation generator 524 may be provided on the handle 610 in addition to or in the alternative to the electrical port 622 on needle assembly 612. For example, as illustrated in FIG. 9, a proximal end of handle 610 may include electrical port 624 for receiving an input from the electrical nerve stimulation generator 524. FIG. 10 illustrates a close up view of the proximal end of housing 610. As can be seen, the distal end of housing 610 may include a status light 626 for the cartridge status, a status light 628 for the needle assembly, a device serial number 630, and/or a reset access 632 in addition to electrical port 624. The one or more input electrical ports 622, 624 may be configured to be electrically coupled with one or more of the electrical stimulation needles of the device 600.

Optionally, in some embodiments, the electrical nerve stimulation generator 524 may be fully integrated with the treatment device. For example, FIG. 11 illustrates yet another exemplary treatment system 634 with a fully integrated electrical nerve stimulation generator 524. The system 634 includes a housing 636 that defines a handle of the device. An electrical adapter 638 may be disposed at the distal end of housing 636 that is configured to electrically couple with a replaceable needle assembly (not shown). Housing 636 may house electrical nerve stimulation generator 524. Electrical nerve stimulation generator 524 may electrically couple with the adapter 638. Adapter 638 may provide an interface between the electrical nerve stimulation generator 524 and a replaceable needle assembly when the needle assembly is coupled with adapter 638.

While the exemplary needle assembly 510 of FIG. 6A is illustrated with a single needle for performing the cooling treatment in addition to the nerve stimulation, it should be understood that other treatment devices or needle assemblies may be provided with a plurality of needles. One of skill in the art will appreciate that two, three, four, five, six, or more needles may be used. When a plurality of needles are used, they may be arranged in any number of patterns. For example, a single linear array may be used, or a two dimensional or three dimensional array may be used. Examples of two dimensional arrays include any number of rows and columns of needles (e.g. a rectangular array, a square array, elliptical, circular, triangular, etc.), and examples of three dimensional arrays include those where the needle tips are at different distances from the probe hub, such as in an inverted pyramid shape. Accordingly, in some embodiments, the integrated cooling and stimulation needle probe may have a plurality of needles for cooling and/or nerve stimulation. For example, FIG. 12 illustrates an exemplary needle assembly 710 that includes a plurality of needles 712 that may perform the method 500 with a plurality of needles according to some embodiments of the disclosure. In use, coolant may flow through one or more of the needles 712 thereby cooling a distal end of the one or more needles 712 and producing a cold zone 721 associated with the needle assembly 710. The needle assembly 710 may have a cooling center 722 that is associated with a center of the cold zone 721 produced by the one or more needles 712. Additionally, at least one of the needles 712 (in the illustrated embodiment, center needle 712 c) may be constructed from an electrically conductive material and may also have an electrically insulated coating 723 disposed about a length of the needle 712 c. The electrically insulated coating 723 may electrically insulate a proximal portion of a length of the needle 712 c that is adjacent the distal end of the housing 714 and may extend toward a distal portion of the length of the needle 712 c. The electrically insulated coating 723 may be a fluoropolymer coating, a silicone rubber coating, a parylene coating, a ceramic coating, an epoxy coating, a polyimide coating or the like. A proximal end of needle 712 c may be uninsulated and may be configured to couple with the electrical nerve stimulation generator 524 of a percutaneous electrical stimulation device, e.g., through a manner described above, such as an electrical port on the needle assembly housing, an electrical port on the treatment device housing, an integrated generator 524 that electrically couples to needle 712 c via an adapter between the device handle and the needle assembly 710 or the like. The portion of needle 712 c that is disposed at the cooling center 722 may be uninsulated such that the intensity of the electric field produced by electrical nerve stimulation generator 524 via needle 712 c may be co-incident with the center of the cold zone 721 that is produced by the needle assembly 710.

While illustrated as including three needles 712, it should be understood that this is exemplary and non-limiting. Two, four, five or more needles may be provided in other embodiments. Further, while illustrated with each of the needles 712 being supplied by a cooling fluid supply tube and thus each of the needles 712 being configured to cool to produce cold zone 721, in other embodiments, only some of the plurality of needles may be configured to provide the cooling treatment. Other needles 712 may be provided separately for electrical stimulation. Accordingly, in some embodiments, center needle 712 may be provided for electrical stimulation only, while the adjacent needles 712 may be provided to produce cold zone 721. Put in another way, in some embodiments, stimulation needle (e.g., needle 712 c) may not include a cold center along the length of the needle, but nevertheless, the cooling center 722 of the cold zone 721 associated with the needle assembly 710 may be disposed along the length of the stimulation needle. Thus, the stimulation needle may provide more accurate targeting of a target nerve with the cold zone 721 whether or not it provides cooling itself.

Additionally, it should be understood that while assembly 710 is illustrated with a single stimulating needle 712 c, additional needles 712 of assembly 710 may be configured to separately stimulate as desired. Accordingly, some or all of the plurality of needles 712 may be configured to provide nerve stimulation. Thus, nerve stimulation generator 524 may be electrically coupled with each stimulating needle.

Further, in some embodiments, an adjacent needle (e.g., needles 712 adjacent to 712 c) may provide an electrical return during nerve stimulation. Accordingly, one or more of the adjacent needles may be constructed from a conductive material and may be uninsulated at a location proximate to an uninsulated portion of an adjacent nerve stimulation needle. Optionally, adjacent needles may also include an electrically insulated coating that extends from a proximal portion of the needle adjacent to the housing toward a distal portion of the needle.

In still further embodiments, during cryoneurolysis delivery 509, nerve stimulation may be conducted to provide feedback to the treatment. For example, in some embodiments, nerve stimulation may be performed continuously and/or concurrently with cryoneurolysis delivery 509 to determine the efficacy of the treatment in real time. Optionally, the nerve stimulation may be repeated in a discrete intervals during cryoneurolysis delivery 509. In such embodiments, cryoneurolysis delivery 509 may continue until there is a cessation of motor function or paresthesia. In some embodiments, cryoneurolysis delivery 509 may be shorter in duration when the nerve stimulation feedback is associated with a successful treatment. In other embodiments, cryoneurolysis delivery 509 may be longer in duration when the nerve stimulation feedback indicates that the nerve has not been successfully treated. Further, initial tests surprisingly suggest that ice ball formation by the treatment needles of the assembly may be produced at a quicker rate when the electrical stimulation is concurrently delivered.

In still further embodiments of the present disclosure, a cryoneurolysis treatment device may be provided with an integrated transcutaneous electrical stimulation device. For example, FIG. 13 illustrates an exemplary treatment system 750 with an integrated transcutaneous electrical stimulation probe 752 according to some embodiments. FIG. 14 illustrates an exemplary operation of the system 750 of FIG. 13 according to some embodiments. Treatment system 750 further includes two cooling treatment needles 754 for insertion through the tissue surface 756 to produce a cooling zone 758 to treat target nerve 760. The transcutaneous electrical stimulation probe 752 may have distal end for providing electrical stimulation through the tissue surface 756 for localizing the target nerve 760. A proximal portion of probe 752 may be coupled with a spring 762. After identifying a location of the target nerve 760, the device 750 may be pressed distally against the tissue surface 756 to insert needles 754 into the tissue. During needle 754 insertion, the spring 762 may compress and the probe 752 may withdraw into the housing of treatment system 750. Thereafter, the needles 754 may deliver cryoneurolysis to produce cold zone 758. Such an embodiment may localize a target nerve transcutaneously and may allow the treatment needles to be inserted into the tissue without having to first interchange the transcutaneous electrical stimulation device for the device with the cooling treatment needles.

FIGS. 15A-18 illustrate yet further aspects and features of a cryoneurolysis treatment device that is adapted to couple with or be integrated (e.g., partially or fully) with a nerve stimulation device according to certain embodiments described herein. Such cold therapy treatment devices may include one or more features, in whole or in part, of any of the embodiments described herein. Both nerve stimulation and cryoneurolysis may be performed or delivered by such a cryo-stimulation device. For example, nerve stimulation and cryoneurolysis may be delivered concurrently or alternately with the cryo-stimulation device. Further, in some embodiments, the device may be operated by a single operator or clinician. Accordingly, such embodiments of the present disclosure may improve nerve targeting during cryoneurolysis procedures. Improvements in nerve localization and targeting may increase treatment accuracy and physician confidence in needle placement during treatment. In turn, such improvements may decrease overall treatment times, the number of repeat treatments, and the re-treatment rate. Further, additional improvements in nerve localization and targeting may reduce the number of needle insertions, applied treatment cycles, and may also reduce the number of cartridge changes (when replaceable refrigerant cartridges are used). Thus, embodiments of the present disclosure may provide one or more advantages for cryoneurolysis treatments by improving localization and treatment of target nerves. Hence, some aspects of the present disclosure provide methods, devices, and systems for localizing, targeting, and treating a nerve with integrated cold therapy and electrical stimulation systems.

An integrated cooling and stimulation needle probe may have a single needle for both cooling and nerve stimulation. For example, FIG. 15A illustrates an exemplary needle probe or assembly 910 having one or more needles 912 extending distally from a housing 914 that may be used to deliver nerve stimulation for localization of the nerve and cold therapy for treatment of the nerve (e.g., the method 500 as described above) according to some embodiments of the present disclosure. Such needles 912 may be configured to deliver bipolar, monopolar, or alternate between bipolar and monopolar electrical stimulation for localizing target nerves for cold therapy treatment. In use, coolant may flow through the needle 912 (e.g. via cooling fluid supply tube or the like) thereby cooling a distal portion of the needle 912 and producing a cold zone 921 associated with the needle 912. The needle 912 may also have a cooling center, as described above with respect to FIGS. 6A-6C and 12 (not shown in FIG. 15A) along the length of the needle 912 that is associated with a center of the cold zone 921 produced by the needle 912. As described in more detail below, in some embodiments, cold zone 921 or cooling center may be located between at least one pair of electrodes (e.g., electrical conductors, contacts, poles, exposed conducting portions) identified individually as electrode 944 and electrode 946 on needle 912.

The needle 912 may be constructed from an electrically conductive material and may also have an electrically insulated coating 923 disposed about a length of the needle 912. The electrically insulated coating 923 may electrically insulate selected or desired portions of the needle 912. For example, coating 923 may insulate a proximal portion of a length of the needle 912 that is adjacent the distal end of the probe or needle assembly housing 914 and may extend toward a distal portion of the length of the needle 912. The electrically insulated coating 923 may be made from a dielectric or other suitable type of insulating material. For example, the coating 923 may be a fluoropolymer coating, a silicone rubber coating, a parylene coating, a ceramic coating, an epoxy coating, a polyimide coating or the like.

One or more regions or portions of the needle 912 may be uninsulated by the coating 923 (e.g., exposed or conductive). For example, a proximal end of needle 512 may be uninsulated and may be configured to couple with an electrical nerve stimulation generator 924 of a percutaneous or transcutaneous electrical stimulation device. The electrical nerve stimulation generator 924 may be integrated with (e.g., positioned on or within) housing 914. In other embodiments, the electrical nerve stimulation generator 924 may be positioned away from housing 914. For example, housing 914 or needle assembly 910 may have a port configured to be coupled to an electrical nerve stimulation generator (e.g., an off the shelf generator). In certain embodiments, a first portion at a distal end of needle 912 and a second portion proximate the first portion may be uninsulated with a third insulated portion extending therebetween (FIG. 15A). The electrodes 946 and 944 may be positioned at the uninsulated first and second portions, respectively. In some embodiments, only the first portion or the second portion is uninsulated. In other embodiments, electrodes 946 and/or 944 may be conductive portions of the needle 912 that are uninsulated or exposed by the coating 923. For example, a distal part of needle 912 (e.g., tip) may be made from electrically conductive material exposed or uninsulated by coating 923. The electrodes 946 and 944 may form a pair of electrodes electrically coupled to electrical nerve stimulation generator 924 for delivering bipolar electrical stimulation to locate target nerves. Using bipolar electrical stimulation may provide improved control over a stimulation region (e.g., size and shape of the region), which may result in improved predictability of location of or proximity to a nerve relative to monopolar electrical stimulation, where the return electrode of a larger surface is located relatively far away from the active electrode. The electrodes or contacts for bipolar stimulation are generally positioned closer together relative to monopolar configurations. Thus, in some embodiments, electric field distribution (and hence the range of the stimulation region) may be significantly controlled by controlling the geometry of each electrode, thereby resulting in improved predictability of the proximity to a target nerve for bipolar electrical stimulation configurations.

The pair of electrodes 946 and 944 may be a cathode and anode, respectively. In other embodiments, electrode 946 is an anode and electrode 944 is a cathode. An electric field 940 is generated by electrical nerve stimulation generator 924 about the pair of electrodes 946, 944. As illustrated in FIG. 15A, electric field strength (depicted by concentration of electric field lines 941) and hence current density are generally highest between the pair of electrodes. As such, a lowest stimulation-current threshold (e.g., minimum current to achieve nerve stimulation) may be detected between the pair of electrodes. Therefore, in certain embodiments, a coldest point in the needle 912 (e.g., cooling zone 921 or the center of cooling zone 921) may be located between the pair of electrodes (e.g., third insulated portion extending therebetween) to deliver cryoneurolysis treatment to a localized nerve (e.g., current threshold corresponding to a desired distance from the target nerve is achieved).

While the exemplary needle assembly 910 of FIG. 15A and others herein are illustrated with a single needle for performing the cooling treatment in addition to the nerve stimulation, it should be understood that other treatment devices or needle assemblies may be provided with a plurality of needles (e.g., as described in more detail above with respect to needle assemblies 510 and 710). One of skill in the art will appreciate that two, three, four, five, six, or more needles may be used and may be arranged in any number of patterns. Accordingly, in some embodiments, the integrated cooling and stimulation needle assembly 910 may have a plurality of needles for cooling, nerve stimulation, or both. In some embodiments, two or more needles of a needle assembly may flank a target nerve. In certain embodiments, one or more needles extending parallel to the first needle include one of the pair of electrodes (e.g., electrode 944, 946) for bipolar or monopolar stimulation. In some embodiments, one or more needles of the needle assembly provide the electrical return for a stimulation circuit.

In some embodiments, while bipolar electrical stimulation may facilitate improved precision for localizing a nerve, it may be beneficial to switch or alternate between bipolar and monopolar modes of electrical stimulation as illustrated in FIG. 15B. For example, monopolar electrical stimulation may be delivered to localize a target nerve within a first distance (e.g., about 10 mm) and then switched to bipolar electrical stimulation to further localize a target nerve within a second distance less than the first distance (e.g., of about 0.5 mm). In this manner, bipolar electrical stimulation may be delivered to further “fine-tune” localization of the nerve after initial monopolar electrical stimulation is delivered to localize the nerve within the first distance.

As illustrated in FIG. 15B, the needle 912 may include a pair of electrodes (identified individually as 946 and 944) as in the embodiment of FIG. 15A, configured to deliver bipolar electrical stimulation. The needle 912 may include a cooling zone, conductive portions, and insulative coating 923 with exposed or uninsulated portions as described above. Further, the pair of electrodes may also be electrically coupled to the electrical nerve stimulation generator 924 for bipolar, monopolar, or both bipolar and monopolar electrical stimulation. For example, an insulated wire 943 a (dashed lines to illustrate return paths) may electrically connect return electrode 944 to the generator 924 and a separate insulated wire 943 b (solid line to illustrate active paths) may electrically connect active electrode 946 to the generator 924 only during bipolar stimulation. It will be appreciated, that wire 943 b may electrically connect electrode 946 to the generator 924 during both monopolar and/or bipolar stimulation and that one or more wires (e.g., wire 943) may be included in any of the embodiments described herein to connect electrodes to an electrical stimulation generator.

As further illustrated in FIG. 15B, a third electrode 947 configured as a return electrode may be positioned on a skin 948 of a patient (e.g., spaced apart or away from the needle 912). In some embodiments, the third electrode may be a patch electrode such as a silver to silver chloride patch. In other embodiments, the third electrode (e.g., a return electrode) may be positioned on or within the housing 914, a needle heater block or component (e.g., as described in more detail below with respect to FIG. 18), or on or within the electrical nerve stimulation generator 924. In certain embodiments, the housing, heater block or component, or nerve stimulation generator itself acts as the third electrode or return. The third electrode 947 is arranged with at least one (e.g., an active electrode) of the pair of electrodes (e.g., electrode 946) and electrically coupled to the electrical nerve stimulation generator 924 via wire 943 a for a return pathway to provide monopolar electrical stimulation for nerve localization. The third electrode 947 may have a substantially larger surface area than the active electrode to better disperse current for reducing or minimizing heat generation from monopolar electrical stimulation. An electric field 942 is generated by electrical nerve stimulation generator 924 between the active electrode 946 and the third electrode 947 via monopolar stimulation for localizing a target nerve (e.g., within a first distance). As described above, electrical stimulation may be alternated or switched between monopolar (for generation of electric field 942) and bipolar stimulation (for generation of focused electric field 940) as desired to localize a target nerve according to embodiments of the present disclosure.

Needle 912 may include any suitable tip configuration. For example, needle 912 may include a substantially symmetrical pyramid or wedge-shaped tip configuration as illustrated in FIG. 15A or an asymmetrical beveled edge as illustrated in FIG. 15B. The pair of electrodes 946, 944 may be positioned in a substantially symmetrical configuration as illustrated in FIG. 15A. In other embodiments, the pair of electrodes 946, 944 may have an asymmetrical configuration as illustrated in FIG. 15B and described in more detail below with respect to FIGS. 16A-16D.

FIGS. 16A-16D illustrate various embodiments of the pair of electrodes 946, 944 with asymmetrical electrode configurations that can be provided with needle probe or assembly 910. For example, needle shape, electrode type, size (e.g., contact surface area), shape (e.g., concave, convex), orientation, location, and/or electrical properties (e.g., capacitance, conductivity) may be varied to provide asymmetrical electrode configurations as described herein. FIG. 16A illustrates an asymmetrical electrode configuration where electrode 944 (e.g., the anode or return electrode) is located on needle 912 as described above. For example, a center of electrode 944 may be aligned with a longitudinal axis of needle 912. However, electrode 946 (e.g., the cathode or active electrode) is located asymmetrically relative to electrode 944 via an asymmetrical needle tip configuration (e.g., a beveled edge). In the embodiment of FIG. 16A, electrode 946 may positioned only at a tip of needle 912 that has an asymmetrical tip configuration (e.g., a beveled edge) rather than a pyramid-shaped symmetrical tip as illustrated in FIG. 15A. For example, the electrically conductive needle 912 may include insulative coating 923 as described above with respect to FIG. 15A. A tip of the beveled distal edge of needle 912 may be exposed from the insulative coating 923 such that a conductive portion (e.g., electrode 946) is exposed at the tip. In such embodiments, electric field 940 is generated with a stimulating region sufficient for nerve localization oriented only on one side of the needle 912 (e.g., where electric field strength is highest) as depicted by the concentration of electric field lines 941 on a right side of the needle 912 in FIG. 16A. In such embodiments, a target nerve would be preferentially stimulated if it was positioned on the right side of the needle 912 with the stimulator 924 generating a minimum current threshold.

FIG. 16B illustrates another asymmetrical electrode configuration according to another embodiment of the present disclosure. The pair of electrodes 944, 946 are located on the needle 912 in an asymmetrical configuration. As described in more detail above with respect to FIG. 15A, the needle 912 may have an insulative coating 923. The pair of electrodes may be positioned at uninsulated or exposed portions of the needle 912. In some embodiments, one or more of the pair of electrodes may be conducting portions of the needle 912 exposed or uninsulated by the coating 923. For example, electrode 946 may be an exposed distal beveled edge of needle 912 as opposed to only the tip as described above with respect to the embodiment of FIG. 16A. Electrode 944 may be an exposed shaft portion of needle 912 located proximally relative to and electrically isolated from electrode 946 (e.g., a dielectric or other insulative material between the two electrodes within the needle 912 to prevent them from shorting together within the needle). Electrode 944 may extend along a side portion of the needle 912 such that a center of the electrode 944 is spaced apart from a longitudinal axis of needle 912. Electrode 946 may be coupled with the electrical nerve stimulation generator 924 with an insulated wire 943 b as described above.

Electric field 940 is generated with a stimulating region oriented on one side of the needle 912 (e.g., where electric field strength is highest) as depicted by the concentration of electric field lines 941 only one a left side of the needle 912 in FIG. 16B. In such embodiments, a right side of electrode 944 may be insulated with the insulative coating 923. Asymmetrically configuring the pair of electrodes may provide directionality as a stimulating region is oriented only on one side of the needle 912. Such directionality may facilitate or provide a binary searching or localizing methodology (e.g., by determining which side of the needle 912 a nerve resides on with each placement or needle insertion) with minimal or reducing needle insertions and withdrawals accordingly. Implementing an asymmetrical electrode design or configuration on a single rotatable needle 912 (e.g., rotatable after insertion into a patient or electrode orientation may be rotated without withdrawal from a patient), allows identification of a direction (e.g., X-Y-Z position) of the nerve with respect to the coldest point in the needle 912 (e.g., cooling zone 921 or the center of cooling zone 921). For example, X and Y directions may be identified by with electrical stimulation and rotation of the needle 912 to determine corresponding distance in each direction. Z direction may be identified by insertion depth of the needle 912.

FIG. 16C illustrates another asymmetrical electrode configuration according to yet another embodiment of the present disclosure. It may be advantageous in certain embodiments to provide a pair of electrodes 944, 946 on the needle 912 with substantially different contact surface areas. For example, contact surface area ratio of the electrodes may range between about 2 to 1 to about 8 to 1. In other embodiments, the ratio is about 4 to 1. A minimum current threshold for electrical stimulation with such electrodes generally occurs near the electrode with the substantially smaller or smallest area. In some embodiments, a current threshold near electrode 946 is about 2, 3, 4, or 5 times the current threshold near electrode 944 or vice versa. This may provide only a single or one stimulating region configured to achieve a distinguished minimum current threshold to localize a target nerve (e.g., where electric field strength and current density are highest as depicted by the concentration of electric field lines 941).

For example, electrode 944 may have a substantially larger surface area relative to electrode 946 located along a beveled distal edge of needle 912. Concentrated electric field lines 941 and hence current density are highest near the electrode 946 with substantially smaller surface area relative to electrode 944. This may provide one stimulating region configured to achieve a distinguished minimum current threshold to localize the target nerve (e.g., proximate electrode 946 on a left side of needle 912). As described above with respect to FIG. 15A, a cold zone may be delivered between the electrodes 944, 946. Providing one stimulating region (e.g., at or near a distal end of the needle 912) may allow a user or clinician to more precisely or accurately position the needle 912 and accordingly, the cold zone relative to a target nerve for treatment. For example, knowing a position of a cold zone relative to the distal edge electrode 946 (e.g., above the one stimulating region), a user or clinician may evaluate whether a cold zone of needle 912 has been inserted past a target zone of the cold zone with respect to a target nerve after the target nerve has been localized.

FIG. 16D illustrates another asymmetrical electrode configuration according to a further embodiment of the present disclosure. In some embodiments, it may be desirable to increase or expand a stimulating region by effectively spreading out generated electric field 940. For example, in certain embodiments, too small of a stimulating region between electrodes may lead to too much current effectively “shorting” between electrodes (e.g., electrodes 944, 946) during stimulation. Reducing the current that is effectively shorting between the electrodes by increasing total current delivery may inadvertently stimulate un-targeted neuromuscular tissue. Therefore, in some embodiments, increasing a stimulating region may be provided by reducing or minimizing a conductive-fluid region between a pair of electrodes (e.g., electrodes 944, 946). This may be achieved by facing one or both of the electrodes away from each other (e.g., oriented or facing opposing directions) and/or by using concave-shaped electrodes (e.g., as electric field lines are perpendicular to a surface of an electrode). As illustrated in FIG. 16C, electrode 946 can extend along a beveled edge tip of needle 912 and face substantially in a first direction. Electrode 944 can extend along a side of the needle 912 such that it faces a second direction substantially opposite the first direction. In this manner, electric field 940 is generated and extends or spreads effectively from one side of needle 912 to an opposing second side of needle 912. A stimulating region may be spread or expanded accordingly.

Any of the asymmetrical electrode configurations of FIGS. 16A-16D may be applied to any of the needle assembly embodiments described herein. Further two or more configurations may be provided or included as desired. As described above, alternating or switching between monopolar and bipolar stimulation may also be provided with such embodiments. Additionally, needle assemblies may be provided with a single needle or multiple needles to delivery stimulation and/or cold therapy. In some embodiments, a needle assembly comprises two needles or more needles. In some embodiments, one needle carries an anode electrode and another needle carries a cathode electrode for bipolar stimulation. In other embodiments, a second and/or third needle flanking a first needle provides the return to the first needle during electrical stimulation of a target nerve. It will be appreciated that the active and return electrodes may be selectable by the user or by the processor of the device. For example, the selection for the return may be based on which needle is closest to the nerve. Likewise, two flanking needles could be selected as the active needles (e.g., double cathode) with the center needle serving as the return needle (e.g., anode).

As described above in more detail with respect to certain embodiments, integrated cold therapy and electrical stimulation systems may provided herein. Such cryo-stimulation devices may include a housing (e.g., housing 914) that defines a handle of the device. Housing 914 may house an electrical nerve stimulation generator 924. Electrical nerve stimulation generator 924 may electrically coupled with a needle assembly (e.g., needle assembly 910) to generate a stimulation signal (e.g., stimulation region, electric field). The stimulation signal may be generated within the cryo-stimulation device. Alternatively, in order to maintain the stimulator generator 924 as a device separate from the cryo-stimulation housing, a stimulation signal may be received from an off-the-shelf generator (e.g., PENS (input)) connected to the cryo-stimulation device via, for example, a port as described in more detail above.

FIGS. 17A-17C illustrate exemplary needle probes or assemblies 1810 having one or more split needles 1812 (identified individually as 1812 a, 1812 b, and 1812 c) that may also be used to deliver nerve stimulation for localization and targeting of the nerve and cold therapy for treatment of the nerve (e.g., the method 500 as described above) according to some embodiments of the present disclosure. The split needles 1812 may include electrodes configured for bipolar and/or monopolar stimulation as described above. The split needles 1812 may include symmetrically and/or asymmetrically configured electrodes. The split needles 1812 may be electrically coupled with an electrical nerve stimulation generator 1824. The electrical nerve stimulation generator 1824 may be integrated with (e.g., positioned on or within) a housing 1814 of the needle assemblies. In other embodiments, the electrical nerve stimulation generator 1824 may be positioned away from housing 1814. For example, the housing 1814 or needle assemblies may have a port configured to be coupled to an electrical nerve stimulation generator (e.g., an off-the-shelf PENS generator).

FIG. 17A illustrates a split needle 1812 a having a first shaft 1872 and a second shaft 1870 extending along (e.g., contiguously) the first shaft 1872. In some embodiments, first shaft 1872 and second shaft 1870 share a boundary or edge. In other embodiments, the first shaft 1872 includes a first edge extending along a second edge of second shaft 1870. While illustrated with the first shaft 1872 on a left side of second shaft 1870, in other embodiments, first shaft 1872 extends along a right side of second shaft 1870. In some embodiments, forming a needle for cryo-stimulation treatments with two shafts rather than a singled integrated shaft may decrease manufacturing costs or improve manufacturability.

The first shaft 1872 may be a conductive shaft configured to deliver electrical stimulation (e.g., from a tip portion) from electrical stimulation generator 1824 to localize a target nerve. In some embodiments, the first shaft 1872 is constructed from an electrically conductive material. The first shaft 1872 may include an insulative coating 1823 as described above with respect to other embodiments. In certain embodiments, the first shaft 1872 is insulated along its length (e.g., length of needle 1812 inserted into a patient). A small portion or area 1874 (e.g., region, tip, edge) at a distal end portion may be conductive (e.g., exposed or uninsulated) and configured to contact a target nerve or be positioned proximate to the target nerve for localizing the target nerve. In the illustrated embodiment, conductive portion 1874 a (e.g., surrounding in broken lines) is a portion of the tip of the beveled edge of the needle 1812 a. In other embodiments, conductive portion 1874 may include a region or area at the end of a tip of the needle (e.g., conductive portion 1874 b as illustrated in FIG. 17B in hatching). In other embodiments, first shaft 1872 may include pairs of electrodes as described above. Further, in some embodiments, first shaft 1872 may retract relative to second shaft 1870. For example, first shaft 1872 may be retracted or removed from a patient when not being used (e.g., after localization of a target nerve and/or during cold therapy). Retraction of the first shaft 1872 may provide improved nerve encapsulation by a cooling zone or cooling center (e.g., ice ball) of the second shaft 1870 as described in more detail below.

Distal ends of the first and second shafts may be aligned to form a substantially continuous distal tip of needle 1812 (e.g., an asymmetric beveled edge (FIGS. 17A-17B), a symmetric pyramid tip (FIG. 17C)). Second shaft 1870 may be configured to delivery cold therapy to a target nerve. Second shaft 1870 may include a distal end and a proximal end and a length extending therebetween. Second shaft 1870 includes a lumen 1838 (e.g., a blind shaft) and a supply tube 1836 disposed at least in part in the lumen 1838. The supply tube 1836 extends distally from a proximal end of the needle 1812 toward a distal end. The exemplary supply tube 1836 comprises a fused silica tubular structure (not illustrated) having a polymer coating, as described previously. A cooling fluid source as described in more detail above may be coupled to the supply tube 1836 to direct cooling fluid flow into a lumen 1834 of the tube 1836 so that liquid from the cooling fluid flow vaporizes within the lumen 1834 to produce a cold zone (e.g., to treat a targeted nerve) with a cooling center which may enable ice ball formation at a target nerve.

FIG. 17C illustrates a split needle 1812 c having three shafts. A first shaft 1872 sandwiched between a second shaft 1870 a and a third shaft 1870 b extending along (e.g., contiguously) opposing sides or edges of the first shaft 1872. Distal ends of the shafts may be aligned to form a substantially continuous distal tip of needle 1812 c. For example, the three shafts may form a pyramid tip as illustrated in FIG. 17C. In other embodiments, the three shafts may be aligned to form a beveled edge. A conductive region may extend along the distal tip (e.g., as identified in broken lines) or include a larger region as illustrated in FIG. 17B. The shafts 1870 a and 1870 b may be configured as shaft 1870 described above to provide cold therapy to a target nerve. Spacing of shafts 1870 a and 1870 b may be optimized such that liquid from the cooling fluid flow that vaporizes within the lumens 1834 to produce cold zones (e.g., to treat a targeted nerve) may enable wider and/or flatter ice ball formation at a target nerve. A wider, flatter ice ball may potentially allow large nerves or larger bundles of nerves to be treated faster. In some embodiments, such larger nerves may be treated with only a single treatment. Additionally, the needle 1812 c may allow improved targeting and/or treatment of the nerve when shaft 1872 is retracted to allow a target nerve to be flanked by the two outer shafts 1870 a and 1870 b and their respective cooling zones or centers (e.g., ice balls).

FIG. 18 illustrates an exemplary embodiment of integrated cold therapy and electrical stimulation cryo-stimulation devices with integrated return of the electrical signal. A needle assembly 1910 includes one or more needles 1912 configured to provide both electrical stimulation and cold therapy. The needle assembly 1910 may include a housing 1914 and an electrical stimulation generator 1924 coupled to the needle 1912. The generator 1924 may be integrated within the housing 1914 or positioned away from the housing 1914 as described in more detail above with respect to other embodiments of the present disclosure. The needle assembly 1910 is configured to localize and treat a target nerve 1984 after insertion through skin 1982 of a patient. The needle assembly 1910 may include a heater assembly 1944 which includes associated components such as a heater block or other thermally responsive element and/or sensors. The heater may heat skin proximal near an insertion region to prevent or reduce unwanted skin damage in the area.

An electrical signal may be generated by the stimulation generator 1924 and travel in a loop as illustrated by the arrows. The signal may travel through the skin (e.g., skin and adipose tissue) of a patient to stimulate and localize the target nerve 1984. In some embodiments, the electrical signal may return through in the heater assembly or components 1944 attached to the heater. The heater components (e.g., heater block) 1944 may be kept in contact with skin of the patient during electrical stimulation. In alternative embodiments, the electrical circuit or signal ground may be integrated or positioned on or within a portion of the housing 1914 or generator 1924. As discussed above, the needle 1912 may include an insulative coating only exposed at a tip of the needle where the electrical signal is desired (e.g., at or near the target nerve). For example, a first electrical contact or electrode may be positioned at the exposed tip of the needle. A second electrical contact or electrode (e.g., return electrode) may be positioned on or within the heater assembly or components 1944 (e.g., heater block, sensor, housing, generator), or on or within the same or different needle if one or more needles. In other embodiments, other electrode or conductor configurations may be provided as discussed in more detail above. For example, the needle 1912 may include bipolar and/or monopolar electrode configurations. Integrated grounding as described above within the stimulation device may provide improved nerve localization because electric field strength is increased due to a shorter return distance to ground (e.g., on or within the cryo-stimulation device itself rather than on skin of a patient). Further, integrating the return electrode may also eliminate a need for an additional electrode or contact on the skin of a patient. A further benefit of utilizing the skin-contacting surface of the heater assembly as the return electrode is that the impedance of this contact as measured by the PENS generator can be used to provide feedback to the user that the skin heater is not in contact with the patient. That is, if the skin warmer is in intimate contact with the patient's skin, then the PENS generator will measure a relatively low impedance (e.g., less than 10 K ohm, less than 5 K ohm, or less than 1 K ohm), but if the skin heater is not in contact with the patient, then the PENS generator will report a high-impedance condition. This impedance indication provides an additional safety benefit for the cryoneurolysis treatment, as it indicates when the heater is not in a position to adequately protect the skin.

One or more computing devices may be adapted to provide desired functionality by accessing software instructions rendered in a computer-readable form. When software is used, any suitable programming, scripting, or other type of language or combinations of languages may be used to implement the teachings contained herein. However, software need not be used exclusively, or at all. For example, some embodiments of the methods and systems set forth herein may also be implemented by hard-wired logic or other circuitry, including but not limited to application-specific circuits, field programmable gate arrays, or the like. Combinations of computer-executed software and hard-wired logic or other circuitry may be suitable as well.

Embodiments of the methods disclosed herein may be executed by one or more suitable computing devices. Such system(s) may comprise one or more computing devices adapted to perform one or more embodiments of the methods disclosed herein. As noted above, such devices may access one or more computer-readable media that embody computer-readable instructions which, when executed by at least one computer, cause the at least one computer to implement one or more embodiments of the methods of the present subject matter. Additionally or alternatively, the computing device(s) may comprise circuitry that renders the device(s) operative to implement one or more of the methods of the present subject matter.

Any suitable computer-readable medium or media may be used to implement or practice the presently-disclosed subject matter, including but not limited to, diskettes, drives, and other magnetic-based storage media, optical storage media, including disks (e.g., CD-ROMs, DVD-ROMs, variants thereof, etc.), flash memory, RAM, ROM, and other memory devices, and the like.

The terms “invention,” “the invention,” “this invention” and “the present invention” used in this patent are intended to refer broadly to all of the subject matter of this patent and the patent claims below. Statements containing these terms should be understood not to limit the subject matter described herein or to limit the meaning or scope of the patent claims below.

The subject matter of embodiments of the present invention is described here with specificity, but this description is not necessarily intended to limit the scope of the claims. The claimed subject matter may be embodied in other ways, may include different elements or steps, and may be used in conjunction with other existing or future technologies. This description should not be interpreted as implying any particular order or arrangement among or between various steps or elements except when the order of individual steps or arrangement of elements is explicitly described.

Different arrangements of the components depicted in the drawings or described above, as well as components and steps not shown or described are possible. Similarly, some features and sub-combinations are useful and may be employed without reference to other features and sub-combinations. Embodiments of the invention have been described for illustrative and not restrictive purposes, and alternative embodiments will become apparent to readers of this patent. Accordingly, the present invention is not limited to the embodiments described above or depicted in the drawings, and various embodiments and modifications may be made without departing from the scope of the claims below. 

What is claimed is:
 1. A cryo-stimulation treatment device, the device comprising: a needle assembly having a proximal portion and a distal portion, the needle assembly configured to produce a cold zone for cryoneurolysis of a target nerve; first and second electrical contacts coupled to the distal portion of the needle assembly and configured to be electrically coupled to an electrical nerve stimulation generator to provide bipolar stimulation, the electrical nerve stimulation generator configured to generate a first electric field about the first and second electrical contacts for electrically stimulating and locating the target nerve.
 2. The treatment device of claim 1, further comprising a handle defined by a housing coupled to the proximal portion of the needle assembly, and wherein the electrical nerve stimulation generator is disposed within the handle housing.
 3. The treatment device of claim 1, further comprising a handle defined by a housing coupled to the proximal portion of the needle assembly, and wherein the external electrical nerve stimulation generator is coupled to an electrical port on the handle housing or the needle assembly.
 4. The treatment device of claim 1, wherein the first electrical contact is an active electrode and the second electrical contact is return electrode.
 5. The treatment device of claim 1, further comprising a third electrical contact spaced apart from the needle assembly and configured to be electrically coupled to the electrical nerve stimulation generator and at least one of the first or second electrical contacts to provide monopolar stimulation, the electrical nerve stimulation generator configured to generate a second electric field about the third electrical contact and the at least one of the first or second electrical contacts for electrically stimulating and locating the target nerve.
 6. The treatment device of claim 5, wherein the third electrical contact serves as a return electrode and the at least one of the first or second electrical contacts serves as an active electrode.
 7. The treatment device of claim 5, wherein the third electrical contact comprises an active or return electrical contact.
 8. The treatment device of claim 5, wherein the third electrical contact is configured to be positioned on skin of a patient, a housing of the treatment device, or a heater block of the treatment device.
 9. The treatment device of claim 5, wherein the second electric field is generated prior to the first electric field.
 10. The treatment device of claim 1, wherein the first and second electrical contacts are located asymmetrically on the needle assembly.
 11. The treatment device of claim 10, wherein a distal end of the needle assembly comprises a beveled edge.
 12. The treatment device of claim 11, wherein the first electrical contact extends along the beveled edge.
 13. The treatment device of claim 12, wherein only a distal tip of the beveled edge is electrically conductive.
 14. The treatment device of claim 10, wherein a contact surface area of the second electrical contact is greater than a contact surface area of the first electrical contact.
 15. The treatment device of claim 15, wherein the first and second electrical contacts face opposing directions.
 16. The treatment device of claim 1, wherein the needle assembly comprises at least one or more needles.
 17. The treatment device of claim 16, wherein the first and second electrical contacts are on or within the one or more needles.
 18. The treatment device of claim 16, wherein the first electrical contact is on or within a heater block of the needle assembly and the second electrical contact is on or within one of the one or more needles of the needle assembly.
 19. A cryo-stimulation treatment device, the device comprising: a needle assembly configured to produce a cold zone for cryoneurolysis of a target nerve, the needle assembly comprising: a first shaft constructed of electrically conductive material and including an electrically insulating coating, the first shaft comprising a proximal end, a distal end, and length therebetween, and wherein the proximal end of the first shaft is couplable with an electrical nerve stimulation generator that generates an electric field for electrically stimulating and locating the target nerve; a second shaft comprising a proximal end, a distal end, and a shaft lumen extending therebetween; and a cooling fluid supply lumen extending distally within the shaft lumen to a distal portion of the shaft lumen of the second shaft.
 20. The treatment device of claim 19, wherein the first shaft is retractable relative to the second shaft.
 21. The treatment device of claim 19, wherein distal ends of the first shaft and the second shaft form a beveled distal end of the needle.
 22. The treatment device of claim 19, further comprising a third shaft, the third shaft comprising a proximal end, a distal end, and a shaft lumen extending therebetween, and wherein the second shaft and third shaft extend axially along opposing sides of the first shaft.
 23. The treatment device of claim 22, wherein the first shaft is retractable relative to the second shaft and the third shaft.
 24. The treatment device of claim 19, further comprising a heating element and a sensor or heater block coupled to the heating element that acts as electrical return during electrical nerve stimulation of the target nerve.
 25. The treatment device of claim 19, further comprising a housing and wherein the housing acts as electrical return during electrical nerve stimulation of the target nerve.
 26. The treatment device of claim 19, wherein a distal end portion of the first shaft is uninsulated by the electrically insulating coating such that the electric field is generated only about the distal end portion of the first shaft to stimulate the target nerve.
 27. The treatment device of claim 26, wherein only a tip of the distal end portion is uninsulated by the electrically insulating coating.
 28. The treatment device of claim 19, further comprising a cooling fluid source couplable to the cooling fluid supply lumen to direct cooling fluid flow into the shaft lumen so that liquid from the cooling fluid flow vaporizes within the shaft lumen to produce the cold zone.
 29. The treatment device of claim 19, wherein the first and second shafts extend contiguously.
 30. A method of treating a nerve, the method comprising: inserting one or more needles of a needle assembly into a tissue of a patient; electrically stimulating the nerve with the needle assembly via bipolar electrical stimulation to localize the nerve within the tissue; and after localizing of the nerve via bipolar electrical stimulation, delivering cryoneurolysis to the nerve with the needle assembly.
 31. The method of claim 30, further comprising electrically stimulating the nerve with the needle assembly via monopolar electrical stimulation prior to electrically stimulating the nerve with the needle assembly via bipolar electrical stimulation to initially localize the nerve within the tissue.
 32. The method of claim 30, wherein electrically stimulating the nerve with the needle assembly via bipolar electrical stimulation to localize the nerve within the tissue includes generating a first electric field about asymmetrically located first and second electrical contacts coupled to the needle assembly.
 33. A cryo-stimulation treatment device, the device comprising: a needle assembly having a proximal portion and a distal portion, the needle assembly configured to produce a cold zone for cryoneurolysis of a target nerve; a first electrical contact coupled to the distal portion of the needle assembly a second electrical contact positioned on a heater assembly of the needle assembly configured to serve as a return electrode, wherein the first and second electrical contacts are configured to be electrically coupled to an electrical nerve stimulation generator to provide electrical stimulation for electrically stimulating and locating the target nerve.
 34. The treatment device of claim 33, wherein the heater assembly comprises a heater block.
 35. The treatment device of claim 33, wherein the heater assembly is configured to provide a confirmation signal that the heater assembly is in contact with a skin surface of a patient.
 36. The treatment device of claim 35, wherein the confirmation signal is an impedance measurement that is below 10 K ohms. 